MIM PhD Program - ETH Z · Welcome to the 8th Student Retreat of the MIM PhD Program Dear...
Transcript of MIM PhD Program - ETH Z · Welcome to the 8th Student Retreat of the MIM PhD Program Dear...
MIM PhD Program Microbiology & Immunology
8th MIM PhD Retreat 27th ‐ 29th of August 2015
Fiescheralp, Aletsch Arena Switzerland
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Contents
Welcome to the 8th Student Retreat of the MIM PhD Program .......................... 3
Program overview ................................................................................................ 4
Detailed program ................................................................................................. 5
Guest speakers ..................................................................................................... 7
Student talk abstracts .......................................................................................... 9
Poster abstracts ..................................................................................................18
Poster session I ...................................................................................................57
Poster session II ..................................................................................................58
Participant details ..............................................................................................60
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Welcome to the 8th Student Retreat of the MIM PhD Program
Dear Participants,
We hope you will enjoy this year`s MIM retreat. The Fiescheralp is a great place to escape from the daily lab routine and get inspired by all the research that is happening within the Graduate School program. The aim of this retreat is manifold. One important aspect is to give you a taste of what other students work on. We want to boost the interaction between different Labs. Therefore, we encourage you to get out most of the poster session and the student talks. For a wider perspective we invited several excellent guest speakers who will talk about the life as a scientist and beyond. The time of lone warriors in science has passed. That is why we see this retreat also as a meeting to socialize with fellow researchers, start new collaborations and friendships. We are looking forward to the following days with great scientific discussion in a relaxed atmosphere. Contact information
In case of emergency or if something needs to be clarified, please feel free to contact any of
us via e‐mail or phone:
Name Mobile phone No. E‐mail
Isabel Barnstorf 0788807873 [email protected]
Julia Rühl 0766101923 [email protected]
Leoni Swart 0763328690 [email protected]
Bernhard Steiner 0763034732 [email protected]
Dagmara Lewandowska 0768244566 [email protected]
Rebecca Higgins 0787380870 [email protected]
Mario Hupfeld 0787367171 [email protected]
Location
Alpenlodge Kühboden
Familie Rickhoff‐Florian
Fiescheralp 1
3984 Fiesch
Phone: +41 (0)27 970 12 20
Homepage: http://www.kuehboden‐fiescheralp.ch/
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Program overview
Time/date Thursday 27th Friday 28th Saturday 29th
7:00 Breakfast
7:30
Departure from Zurich HB
8:00 8:25 cable car up
8:30 Student session 2
9:00 Dr. Christoph Burkhart Breakfast
9:30
10:00 Coffee break
Hike & Lunch
10:30
Student session 3 11:00 Arrival & welcome
11:30
12:00 Lunch Lunch
12:30
13:00 13:25 cable car up Student session 4
13:30 Student session 1
Workshops: Dr. Urs Ziegler 14:00 Dr. Steve Pascolo
13:56 departure from Fiesch
14:30
15:00 Coffee break Coffee break
15:15
Dr. Heike Nowag 15:30 Introduction into glaciers
16:00 16:25 cable car down
16:30 16:25 cable car down
17:00 Dinner Dinner
17:30
18:00 18:15 cable car up
Socializing time 18:30
Poster session I 19:00
19:30 19:45 cable car up
20:00
Poster session II
Party
20:30
21:00
21:30 22:00 cable car down
22:00
22:30 22:00 cable car down
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Detailed program
Thursday, 27th of August
7:30 Departure Zurich HB
11:00 – 12:00 Arrival & welcome
12:00 – 13:00 Lunch
13:25 Going up with cable car
***************************************** Lecture session 1 *******************************************
Chair: Julia Rühl
13:45 – 14:05 Student talk 1: Dagmara Lewandowska
14:05 – 15:05 Guest Lecture I: Dr. Steve Pascolo, USZ, Miescher Pharma GmbH
15:05 – 15:15 Coffee break
15:15 – 16:15 Guest speaker II: MIM Alumni Dr. Heike Nowag, Consulting PWC
16:25 Going down with cable car
17:00 – 18:00 Dinner
18:15 Going up with cable car
18:30 – 20:00 Poster session 1 (A‐L)
20:00 – 21:30 Poster session 2 (M‐Z)
22:00 Going down with cable car
Friday, 28th of August
7:00 – 8:00 Breakfast
8:25 Going up with cable car
***************************************** Lecture session 2 *****************************************
Chair: Dagmara Lewandowska
8:30 – 8:50 Student talk 2: Weronika Barcik
8:50 – 9:10 Student talk 3: Franziska Schönherr
9:10 – 10:10 Guest Lecture III: Dr. Christoph Burkhart, Novartis Institutes for BioMedical
Research, Department Autoimmunity, Transplantation and Inflammation
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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10:10 – 10:40 Coffee break
***************************************** Lecture session 3 *******************************************
Chair: Rebecca Higgins
10:40 – 11:00 Student talk 4: Emanuel Stiegeler
11:00 – 11:20 Student talk 5: Michel Crameri
11:20 – 11:40 Student talk 6: Isabel Barnstorf
11:40 – 12:00 Student talk 7: Monica Loi
12:00 – 13 00 Lunch
***************************************** Lecture session 4 *******************************************
Chair: Mario Hupfeld
13:00 – 13:20 Student talk 8: Corinna Landig
13:20 – 13:40 Student talk 9: Bernhard Steiner
13:45 – 15:00 Workshops: Dr. Urs Ziegler, Center for Microscopy and Image Analysis
15:00 – 15:30 Coffee break
16:25 Going down with cable car
17:00 – 18:00 Dinner
18:00 – 19:30 Socializing/free time/rest
19:45 Going up with cable car
20:00 – 22:00 Party
22:00 Going down with cable car
22:00 ‐ ??? Party goes on in the restaurant
Saturday, 29th of August
9:00 – 10:00 Breakfast
10:00 – 12:30 Hike
13:56 Train back to Zurich
17:00 Arrival at Zurich HB
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Guest speakers
Steve Pascolo, PhD
Group leader
Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland Phone: +41 44 6342876 [email protected] Performing research leads eventually to inventions or discoveries that can be turned into patents.
Those can be licensed to companies or used as a cornerstone to create a biotechnology company
stemming from University: a spin‐off. By founding a company you have the advantage of creating your
own carrier opportunities, keeping in touch with university research and making links to industry. As
examples of possible paths, I will present the history of two different models of spin‐off that I (co‐)
created: CureVac GmbH in 2000 and Miescher Pharma GmbH in 2008. Thereby, I will introduce the
basic requirements and mechanisms that may help you setting your own company based on your (or
other’s) academic research results.
Heike Nowag, PhD Consultant ‐ Life Sciences & Pharmaceuticals
PricewaterhouseCoopers AG
Birchstrasse 160 | Postfach | CH‐8050 Zürich
http://www.pwc.ch
Phone: +41 79 574 5343
I completed my PhD at the University of Zurich in the field of Immunology in August last year, and was
faced with the decision on what to do next. I decided to leave the world of academia and took a
consulting position with PwC. In my presentation, I want to talk a little about the firm and what it is
like to work as a consultant in the field of Life Sciences & Pharmaceuticals. I would also like to share
my experience on making the transition to industry and useful lessons I have learned along the way.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Dr. Christoph Burkhart, PhD
Director
Department of Autoimmunity, Transplantation and Inflammation
Novartis Institutes for BioMedical Research, Basel, Switzerland
Phone: +41 79 7987523
The presentation will contain a time‐lapse view of my academic and professional career followed by
an introduction to my current workplace, the Novartis Institutes for BioMedical Research (NIBR). NIBR
is a global research organization with about 6,000 scientists dedicated to the discovery of truly
innovative drugs. It focusses on molecular pathways shared by various diseases and integrates clinical
insights with mechanistic understanding of pathological processes.
Drug discovery and drug development at Novartis will be exemplified by the journey of a compound,
the anti‐IL‐17‐specificmonocolobal antibody Secukinumab, from preclinical testing to Proof‐of‐
Concept and beyond. Finally, the possibilities of careers at Novartis through the NIBR Postdoctoral
Program will be described.
Urs Ziegler, PhD
Head of Center for Microscopy and Image Analysis, UZH
Center for Microscopy and Image Analysis, University of Zurich
Winterthurerstrasse 190, CH‐8057 Zürich
Phone: +41 44 635 53 55
Taking a deep look: modern microscopy technologies
Microscopy is widely used in life science. Progress in technology, but also in biology, keeps widening its scope and applications. The very basic theoretical background of light‐ and electron microscopy will be discussed. State of the art and upcoming imaging concepts in light and electron microscopy are summarized. Specifically, the focus will be on confocal laserscanning, light sheet and multiphoton microscopy but also transmission and scanning electron microscopy. All techniques will be discussed with a view on most widely used model organisms or samples. Preparation strategies for samples will be mentioned where appropriate.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Student talk abstracts
Microbiota‐Derived Histamine ‐ Relevance to Mucosal Immune Homeostasis
Weronika Barcik, Remo Frei, Liam O`Mahony
University of Zurich, Swiss Institute of Allergy and Asthma Research, Obere Strasse 22, 7270, Davos
Platz, Switzerland
Histamine is an important immunomodulator. It can influence protective or pro‐inflammatory immune
responses. In addition to host cells, histamine is also secreted by many different bacterial strains. In
this study, the aim is to determine the biological role, pathological significance and therapeutic
potential of bacterial‐derived histamine.
After PCR screening fecal samples from 160 patients and healthy volunteers we observed that the
bacterial HDC gene copy number was significantly higher in asthma patients compared to healthy
volunteers. Moreover atopic asthma patients had significantly increased bacterial HDC gene copy
number compared to non‐atopic patients. In order to identify the bacteria, which secrete histamine,
fecal samples were cultured on TSA plates supplemented with histidine. HDC gene expression by
isolated microbes was confirmed using RT‐PCR and histamine secretion into culture supernatants was
confirmed by ELISA. 16s sequencing of histamine secreting microbes is currently underway. Finally,
invariant natural killer T (iNKT) cells are important for appropriate mucosal immune responses. We
have shown that histamine modulates iNKT cell cytokine secretion and proliferation, raising the
possibility that bacterial‐derived histamine may influence iNKT cell activity at mucosal sites.
In conclusion, we have confirmed that bacteria present within the gut microbiome can secrete
histamine. Bacterial‐derived histamine may have clinical relevance as increased levels of these bacteria
are present within the microbiome of atopic asthma patients.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Impact of persistent viral infections on immune responsiveness in mice
Isabel Barnstorf, Annette Oxenius Institute of Microbiology, Department of Biology, ETH Zurich, Zurich, Switzerland [email protected] Immune responsiveness of a host towards microbial challenges or vaccines depends on the various
constituents of the immune system which are continuously modulated for instance by
the previous infection/vaccine history of an individual, the constant encounter with commensal
microorganisms at mucosal surfaces (the "microbiome") and the exposure of the immune system to
persistent viral infections (the "virome"). Persistent viral infections are wide‐spread in the human
population with estimated 8‐12 persistent viral infections per individual. Yet, in contrast to the
"microbiome", there is currently limited knowledge on how these persistent infections impinge on
immune homeostasis or immune responsiveness.
The aim of this project is to address the influence of two well‐defined persistent viral infections in the
mouse, Lymphocytic Choriomeningitis virus (LCMV) and murine cytomegalovirus (MCMV) on the long‐
term composition, phenotype and function of diverse innate and adaptive immune cells and how such
alterations affect vaccine efficacy, susceptibility to infection by heterologous pathogens,
predisposition to autoimmunity and immunological ageing.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Influenza A virus NS1 inhibits interferon‐mediated signaling independently of its block of general host gene expression
Michel Crameri and Jovan Pavlovic Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, CH‐8057 Zürich, Switzerland [email protected]
Type I interferons (IFNs) act as the first line of defense against viral infections. Upon secretion and
receptor binding, they initiate a signaling cascade that eventually leads to the establishment of an
antiviral state owing to the production of IFN‐induced effector proteins. The type I IFN signaling
cascade involves phosphorylation of signal transducer and activator of transcription 1 (STAT1) and
STAT2. Phosphorylated STATs heterodimerize and translocate to the nucleus, where they activate
transcription of IFN‐responsive genes. Previous studies have shown that influenza A virus (IAV)
infection causes disruption of IFN‐mediated signaling. Using a luciferase‐based reporter assay, we
found that overexpression of avian IAV non‐structural protein 1 (NS1) causes a dramatic reduction of
IFN‐induced gene expression. However, STAT1 phosphorylation was not affected. Instead,
immunofluorescence data demonstrated that NS1 interferes with IFN‐induced nuclear translocation
of STAT proteins. We then assessed whether NS1 proteins from multiple IAV strains differ in their
ability to suppress the signaling events in response to IFN. Intriguingly, most human and avian NS1
proteins which failed to inhibit general host gene expression remained effective IFN signaling
antagonists. In addition, mutation of NS1 residues essential for interaction with CPSF30 and
subsequent block in host mRNA maturation restored general gene expression, while still interfering
with IFN‐mediated signaling. Conversely, disruption of a conserved putative protein‐protein
interaction motif partially restored IFN signaling reporter activity. Taken together, we show that IAVs
have evolved multiple strategies to inhibit IFN‐mediated signaling, relying on both general and specific
suppression of host gene expression.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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The human‐specific pathogen Neisseria gonorrhoeae engages innate immunoregulatory Siglec receptors in a species‐specific manner
Corinna Landig1,2, Jerry Fong2, Sarika Agarwal3, Flavio Schwarz2, Markus Aebi1, Victor Nizet2, Sanjay Ram3 and Ajit Varki2 1Institute of Microbiology, Department of Biology, ETH Zurich, 8093 Zurich, Switzerland; 2Glycobiology Research and Training Center, Departments of Medicine, Pediatrics and Cellular and Molecular Medicine, UC San Diego, La Jolla, CA 92093, USA; 3Department of Medicine, University of Massachusetts Medical School, Worcestor, MA 01605, USA [email protected] The human‐specific pathogen Neisseria gonorrhoeae causes the sexually transmitted disease
gonorrhea, which is a major global health burden and causes serious sequelae like infertility, especially
in women. It has been predicted that the recent vast increase in antibiotic‐resistant gonococcal strains
will lead to an upcoming era of untreatable gonorrhea. The pathogen has evolved different
mechanisms to evade the host immune system. One mechanism is the sialyation of its surface
lipoligosaccharide, which is known to generate resistance to the alternative pathway of complement,
as well as to mask underlying antigenic epitopes. The CD33‐related sialicacid binding immunoglobulin
like lectins (CD33rSiglecs) on innate immune cells recognize sialic acid bearing glycans, thus inducing
either anti‐inflammatory or proinflammatory responses. Based on precedents with other pathogens,
it is likely that anti‐inflammatory Siglecs are targeted by gonococci to exploit the host immune system,
and that pro‐inflammatory Siglecs represent a host evolutionary response to this exploitation.
We now show for the first time that N. gonorrhoeae can engage multiple human CD33rSiglecs that it
might encounter in the genitourinary tract, and that it preferentially bind human Siglecs over the
chimpanzee orthologs. These results can contribute to understanding of the mechanisms utilized by
N. gonorrhoeae to evade the host immune system and potentially to the development of novel
therapeutics to treat gonorrhea.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Resolution of undefined aetiology of respiratory infections in lung transplant patients with unbiased metagenomic sequencing
D. Lewandowska1, B. Ruehe1*, P. Schreiber2*, O. Zagordi1*, F. D. Geissberger1, M. Schuurmans3, A. Zbinden1, J. Böni1, C. Benden3, N. Müller2#, A. Trkola1#, M. Huber1#
1 Institute of Medical Virology, University of Zurich, Zurich, Switzerland; 2 University Hospital Zurich, Division of Infectious Diseases, Zurich, Switzerland; 3 University Hospital Zurich, Division of Pulmonary Medicine, Zurich, Switzerland; * and # contributed equally
Lung transplanted patients are a vulnerable group of immunocompromised individuals prone to
respiratory infections, necessitating a tight monitoring of viral infections post‐transplantation to
prevent respiratory complications and allograft dysfunction. Despite routinely testing for the most
common respiratory viruses, a considerable fraction of infections remains with unknown aetiology.
We re‐analysed samples collected from symptomatic lung transplant patients for which no viral or
microbial aetiology could be found. We used metagenomic approach to identify potential pathogenic
viruses responsible for the respiratory symptoms. For metagenomic sequencing, virus particles were
enriched from respiratory swabs, total nucleic acids extracted and randomly amplified. Sequencing
libraries were prepared and sequenced on MiSeq, Illumina. Quality filtered reads were cleaned from
non‐viral reads by an in‐house bioinformatics pipeline and blasted against a database containing
approximately 40,000 viral genomes. The metagenomic approach identified 3 cases of Rhinovirus A,
Rhinovirus B and Coronavirus HKU. In 4 of the 13 samples we detected HHV‐7 reads in the respiratory
swabs which may have contributed to the observed disease patterns. In addition, we found Torque
Teno virus and bacteriophage reads. Identified Streptococcus pneumoniae phage reads suggested a
previously not defined infection. Metagenomic approaches can identify microbial pathogens in a single
analysis. Our study confirmed low‐level infections with known respiratory viruses and additionally
identified cases of HHV‐7 infection. No other viruses were found in the remaining symptomatic lung
transplant patients leaving the exact aetiology of infection still unclear. This study highlights the
potential of metagenomic sequencing in complex diagnostic situations such as in
immunocompromised hosts.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Regulation of MHC class I endocytosis by the macroautophagy machinery
Loi M.1, Gannagé M.1,2, Lippmann A.1, Becker A.3, Dengjel J.3, Münz C.1
1Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Switzerland; 2Department of Pathology and Immunology‐School of Medicine, University of Geneva, Switzerland; 3Freiburg Institute for Advanced Studies (FRIAS), School of Life Science (LifeNet), University of Freiburg, Freiburg, Germany.
Macroautophagy is a catabolic process that maintains cellular homeostasis by targeting cellular
organelles and cytoplasmic constituents for lysosomal degradation. Additionally, it is involved in
various aspects of immunity including the clearance of pathogens, survival of immune cells and,
importantly, in pathways of antigen presentation. Recently, it has been described to play a role in the
trafficking of plasma membrane proteins.
Here, we show that immortalized macrophages and dendritic cells (DCs) derived from mice
conditionally depleted for an essential macroautophagy protein in their DC compartment (CD11c‐cre
x ATG5fl/fl mice) express increased MHC class I cell surface levels compared to their autophagy
sufficient counterparts. While MHC class I expression and antigen processing seem unaffected, MHC
class I molecules are stabilized on the cell surface of macroautophagy deficient cells due to decreased
internalization and degradation. Moreover, in ATG5+/+DCs treated with chloroquine the total amount
of MHC class I protein is stabilized, significantly reducing the difference in cell surface MHC class I
expression between ATG5‐/‐ and ATG5+/+ cells. This strongly suggests a degradative role of
macroautophagy proteins for MHC class I molecules after internalization.
More interestingly, macroautophagy‐driven stabilization of MHC class I in antigen presenting cells
enhances CD8+ T cell priming during influenza A virus infection in ATG5CD11c mice, resulting in
decreased pathology.
We are currently characterizing the mechanisms that lead to MHC class I stabilization in the absence
of macroautophagy. The understanding of this process may provide important implications for
therapeutic approaches aimed at improving the adaptive immune response against viral pathogens.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Fungal determinants govern the host response to c.albicans in the oral mucosa
Franziska Schönherr1,2, K. Trautwein‐Weidner1,4, F. Kirchner1,4, A. Gladiator1,4, C. Fragoso‐Corti2, O. Petrini3 and S. LeibundGut‐Landmann1
1Institute of Microbiology at ETH Zürich and Institute of Virology at University of Zürich, Switzerland; 2Laboratorio di microbiologia applicata, SUPSI, Bellinzona, Switzerland; 3POLE Pharma consulting, Breganzona, Switzerland; 4equal contribution
The opportunistic fungal pathogen Candida albicans is a member of the normal human microbiota, but
it can cause severe infections in immunocompromised individuals. It is generally believed that the host
immune status determines the outcome of the interaction between the fungus and the host, resulting
in either health or disease. IL‐17 mediated immunity has emerged as a critical mechanism of the host
to regulate the antimicrobial response, thereby limiting fungal overgrowth at the epithelial barriers.
Complementarily, neutrophils contribute to host defense by preventing systemic dissemination of the
fungus.
In a mouse model of oropharyngeal candidiasis the IL‐17 and neutrophil responses are strongly
activated during infection with C. albicans strains SC5314 and both mechanisms account for the rapid
control of the fungus. We explored how the capacity of the fungus to induce these characteristic
responses can affect the infection dynamics. For this, we compared the host response to different
clinical isolates of C. albicans and found that weak IL‐17 and neutrophil responses resulted in persistent
colonization of the oral mucosa by C. albicans and in delayed fungal clearance. However, IL‐17 and
neutrophils remained essential for preventing fungal outgrowth. These findings thus emphasize how
important fungal determinants are to define the host‐pathogen interaction in vivo, which regulates
host colonization versus infection.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Host GTPase machinery implicated in the formation of Legionella‐containing vacuoles
Bernhard Steiner1, Christine Hoffmann2, and Hubert Hilbi1,2
1Institute of Medical Microbiology, University of Zurich, Zürich, Switzerland; 2Max‐von‐Pettenkofer‐Institute, Ludwig‐Maximilians‐Universität Munich, Germany.
Undermining host vesicle trafficking machinery is pivotal for survival and pathogenesis of many
intracellular pathogens. One model organism for studying host cell process modulation during
infection is the Gram‐negative accidental human pathogen Legionella pneumophila, which can cause
a severe pneumonia termed Legionnaires` disease. L. pneumophila injects approximately 300
“effector” proteins into host cells through its Icm/Dot type IV secretion system (T4SS), in order to
guarantee intracellular growth in a distinct pathogen compartment termed the “Legionella‐containing
vacuole” (LCV).
Our recent proteomics studies of purified LCVs from infected Dictyostelium discoideum amoebae or
murine RAW 264.7 macrophages identified 13 small GTPases of the Rab family, implicated in the
secretory or endosomal vesicle trafficking pathways. Using fluorescence microscopy, 6 novel Rab
proteins were confirmed to localize on LCVs harboring wild‐type but not ΔicmT mutant L. pneumophila.
Individual depletion of 20 GTPases by RNA interference indicated that endocytic GTPases (Rab5a,
Rab14 and Rab21) restrict intracellular growth of L. pneumophila, whereas secretory GTPases (Rab8a,
Rab10 and Rab32) implicated in Golgi‐endosome trafficking promote bacterial replication. The down‐
stream effectors and functional roles of these GTPases during L. pneumophila infection and LCV
formation are only incompletely understood. The LCV proteomics analysis also suggested that large
GTPases implicated in vesicle fusion and fission are candidate LCV components. Current experiments
aim at the validation of the proteome data and an investigation of the functional roles of these host
factors for L. pneumophila phagocyte infection and LCV formation. Thus, the phagocyte proteomes of
purified LCVs are a valuable resource for further hypothesis‐driven investigations of the complex
process of pathogen vacuole formation.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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DARPins as Alternative to HIV‐1 broadly Neutralizing Antibodies
Emanuel Stiegeler1, Nikolas Friedrich1, Mustafa Can Eroglu1, Thomas Reinberg2, Mylène Morin3, Yufan Wu2, Jonas V. Schäfer2, John Robinson3, Andreas Plückthun2, Alexandra Trkola1
1Institute of Medical Virology, University of Zurich, Zurich, Switzerland; 2Institute of Biochemistry, University of Zurich, Zurich, Switzerland; 3Institute of Organic Chemistry, University of Zurich, Zurich, Switzerland
Designed Ankyrin Repeat Proteins (DARPins) are small synthetic binding proteins characterized by
exceptional biophysical properties, high target affinities and specificities as well as low production
costs. We previously utilized the DARPin technology to derive HIV‐1 gp120‐V3‐loop reactive clones
with clade B restricted neutralizing activity and a novel, structure‐dependent recognition mechanism
which overcomes HIV envelope shielding. Expanding on our previous finding we here describe the
generation of broadly neutralizing DARPins targeting the V3 loop and membrane proximal external
region (MPER) within HIV‐1 envelope subunit gp41. V3 specific DARPins that possess neutralization
breadths comparable to V3 specific broadly neutralizing antibody (bNAb) PGT121 were isolated. These
clones recognize the V3 loop tip with varying structural preferences. MPER specific DARPins that match
or even exceed the neutralization breadth of bNAbs were generated, though their neutralization
potency still leaves room for improvement. These DARPins bind their target with affinities in the
nanomolar range in a structure dependent manner and act post CD4 engagement to block viral entry.
Our findings underline the potential of the DARPin technology as tool to develop HIV‐1 entry inhibitors
and to gather structural insights on epitope targets which can potentially be used for vaccine design.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Poster abstracts
Role of retrograde transport and RidL for intracellular replication of Legionella
Kevin Bärlocher, Ivo Finsel & Hubert Hilbi
University of Zürich, Institute of Medical Microbiology, Gloriastrasse 30/32, CH‐8006 Zürich, Switzerland
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Structural and functional analysis of lipoprotein glycosylation in fast‐ and slowgrowing mycobacteria
Katja Becker & Peter Sander
University of Zürich, Institute of Medical Microbiology, Gloriastrasse 30/32, 8006 Zürich
With approximately 1,3 million death per year tuberculosis (TB), caused by the bacterial pathogen
Mycobacterium tuberculosis, remains one of the most deadly infectious diseases worldwide (WHO). It
is estimated that 1/3 of the world`s population is latently infected with the bacterium which possesses
a unique and almost impermeable cell envelope. Lipoproteins are abundant in this mycobacterial cell
envelope which enables M. tuberculosis to persist in its human host. They fulfil crucial roles in cell
homeostasis and virulence. Next to their lipidation, many mycobacterial lipoproteins possess glycan‐
moieties but the structure and functions of this second post‐translational modification are unknown.
LppX, LpqW and RpfB are glycosylated lipoproteins involved in cell wall synthesis, virulence and
resuscitation. They will be used as a model for the about 100 lipoproteins in M. tuberculosis. In this
project, the glycosylation sites and structures of these mycobacterial model proteins will be
determined. The function of specific glycan‐moieties on protein localization, stability and function will
be elucidated by mutating glycosylation sites and by assessing the recombinant bacilli in functional
assays. M. smegmatis, a fast‐growing, saprophytic mycobacterium, will be used to identify
glycosylation sites. For functional assays, however, the mutated proteins will be expressed in M. bovis
BCG, a slow‐growing mycobacterium closely related to M. tuberculosis. Virulence assays will be
performed in human macrophages with the M. bovis BCG strains deficient for lipoprotein glycosylation
at specific sites. Results obtained during this project will contribute to the general understanding of
the regulation of cell wall integrity and host‐pathogen interaction.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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In vivo imaging of Salmonella invasion by electron cryotomography
Desiree Böck
ETH, D‐Biol, Institute of Molecular Biology and Biophysics, Otto‐Stern‐Weg 5, HPK D9, 8093 Zürich
Salmonella is an intracellular pathogen that causes significant morbidity and mortality in both humans
and animals. Salmonellosis is one of the most common food‐borne diseases worldwide, however, its
underlying molecular mechanisms are still not completely understood.
The aim of this project is to provide a better understanding of Salmonella invasion into eukaryotic host
cells – a critical step during eukaryote infection – using electron cryotomography (ECT). ECT is cutting‐
edge electron microscopy technique that allows imaging of cells in a near‐native state. Besides, it has
the potential to bridge and integrate observations from structural (atomic scale) and infection biology
(micron scale). Our plan is first to establish a workflow to allow for imaging of eukaryotic cells. This
approach will then be used to investigate the individual stages of Salmonella invasion.
Salmonella wild‐type and mutants will be imaged to elucidate the number of T3SS per cell and their
polarity towards the host cell. A specific mutant that stalls invasion at the point of host attachment
will be used to study T3SS‐contact sites on the host cell and the translocon structure. In particular, a
desired outcome is to image invasion at the point of bacterial attachment and entry to visualize actin
cytoskeletal rearrangements in the host cell.
This interdisciplinary approach has the potential to produce groundbreaking insights into Salmonella
pathogenesis. Furthermore, it could also prove useful for the investigation of bacterium‐eukaryote
interactions involving other pathogens or symbionts in the future.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Expression and characterization of the Plasmodium falciparum & Entamoeba histolytica
Oligosaccharyltransferase
Nathalie Cornillie & Markus Aebi
Institut f. Mikrobiologie, HCI F 412 Vladimir‐Prelog‐Weg 1‐5/10 8093 Zürich
N‐linked glycosylation is one of the most common covalent protein modifications in eukaryotes and
occurs in all three domains of life. This highly conserved process takes place in the endoplasmic
reticulum (ER), where the central step is catalyzed by a large transmembrane protein complex, called
the oligosaccharyltransferase (OST). In eukaryotes, the OST mediates the transfer of a pre‐assembled
lipid‐linked oligosaccharide (LLO) to asparagine residues on nascent polypeptides within the consensus
sequence asparagine‐X‐serine/threonine (N‐X‐S/T), where X can be any amino acid except proline. This
research project focuses on the OST complexes of Plasmodium falciparum and Entamoeba histolytica,
which are predicted to consist of four subunits (Stt3, Wbp1, Ost2 and Ost1). The objective of the
project is to express the OST complexes using the baculovirus/insect cell system, and to purify the
complexes for functional and structural characterization. E. histolytica and P. falciparum differ with
respect to the N‐glycans that are added on proteins in the ER. P. falciparum is missing most of the
glycosyltransferases involved in assembly of the lipid‐linked precursor. Therefore, the OST transfers an
oligosaccharide consisting of only one or two GlcNac residues. In E. histolytica the N‐glycans are
unprocessed Man5GlcNac2 structures lacking a terminal glucose residue, which is a critical substrate
recognition determinant for the OST. The enzymatic activity of the OST complexes will be characterized
by an in vitro N‐glycosylation assay using synthetic fluorescently labeled acceptor peptides and LLOs.
Finally, the OST complexes will be used in structural studies with cryo‐electron microscopy.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
22
The evolution of N332 glycan site directed broadly neutralizing antibodies in HIV infection
Ebner Hanna1, Rusert Peter1, Schanz Merle1, Huber Michael1, Kuster Herbert2, Weber Jacqueline1, Uhr Therese1, Zagordi Osvaldo1, Braun Dominique2, Günthard Huldrych F.1, 2, Trkola Alexandra1
1University of Zürich, Institute of Medical Virology, Winterthurerstrasse 190, 8057 Zürich; 2University Hospital Zürich, Division of Infectious Diseases and Hospital Epidemiology, Rämistrasse 100, 8091 Zürich
Broadly neutralizing antibodies (bnAbs) are considered as vital components of protective vaccines
against HIV‐1 and potential HIV‐1 therapeutics. In natural infection antibodies with broad neutralizing
activity are elicited only in 10‐20% of patients. Understanding the parameters that steer bnAb
responses is thus needed to guide vaccine design. Here we report on bnAb evolution in a participant
of the Zurich Primary HIV Infection study. The patient, ZPHI46, had a slow progressing subtype B
infection and maintained a viral set point of 16600 RNA copies/ml and a geometric mean CD4 T‐cell
count of 450 cells/μl over a period of 9 years in absence of antiretroviral therapy. Longitudinal
assessment of plasma neutralizing antibody activity against autologous virus isolated from consecutive
time‐points showed a prototypic picture of continuous escape. Interestingly, the patient developed
high heterologous breadth neutralizing 70% (29 of 42) of virus isolates from different genetic subtypes
at plasma titers higher than 1:100. Autologous virus isolates resistant to contemporaneous plasma
lacked the N332 glycosylation site, a key bnAb‐target, raising the possibility that bnAb activity in ZPHI46
is directed to this site. Comparison of neutralization activity against virus strains that either contain or
lack the N332 glycan revealed dependence of ZPHI46 activity on this glycan. To study the ontogeny of
this bnAb we have isolated monoclonal antibodies. One clone, ZPHI46.1, proved to capture the N332
restricted potency of the plasma response. A detailed analysis of breadth, epitope specificity and
evolution of this bnAb by NGS based Ig repertoire tracking is underway.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
23
Asymmetric cell division and barrier function in T cell fate determination Hyuliya Ismail Emurla, Annette Oxenius HCI, Wolfgang‐Pauli‐Strasse 10/Vladimir‐Prelog‐Weg 4, CH‐8093 Zurich, Switzerland [email protected] T lymphocyte is the class of immune cells conduct adaptive immune responses. T cells express antigen
specific surface receptors called TCRs. Antigen presentation driven clonal expansion that drives cell
differentiation and cell proliferation, leads development of population of T cells exerting different
transcription profiles in addition to different cellular functions. Asymmetric cell division is a proposed
mechanism to explain differential fate acquisition of T cells as early as first mitotic division followed by
activation of naïve T cells. Asymmetry introduced by formation of stable immune synapse that includes
immune synapse components in addition to polarity associated factors. T‐bet, a master regulator of T
cell differentiation is showed being unequally partitioned by unequal proteasome localization in APC
distal, and APC proximal daughter cells trough asymmetric cell division. The mechanism, called
“Diffusion Barrier”, showed to be responsible for ER compartmentalization between mother and bud
in yeast through asymmetric cell division. In this study, whether T cells form diffusion barrier through
asymmetric cell division, whether diffusion barrier is involved in unequal partitioning of cell fate
determination factors, and whether it is possible to modulate the strength of the barrier or diffusion
barrier function in general respect to the purpose of manipulating determination of cell fate in naïve T
cells, as well as differentiated subtypes of T cells are the focus of extensive scientific examination.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
24
Purification and characterization of the octameric oligosaccharyltransferase from Saccharomyces cerevisiae
Jillianne Eyring & Markus Aebi
Institut f. Mikrobiologie, Vladimir‐Prelog‐Weg 1‐5/10, 8093 Zürich
Asparagine‐linked glycosylation (N‐glycosylation) of proteins is one of the most common covalent post‐
translational protein modifications in eukaryotes and is highly conserved throughout all three domains
of life. The central step of N‐glycosylation is catalyzed by the oligosaccharyltransferase (OST) enzyme
which transfers a pre‐assembled lipid‐linked oligosaccharide (LLO) onto an asparagine residue on
proteins, most commonly within the conserved consensus sequon Asn‐X‐Ser/Thr, where X can be any
amino acid except for proline. In animals, plants and fungi, OST is a heterooligomeric complex
consisting of up to eight non‐identical subunits, all of which are integral membrane proteins. The OST
complex from the budding yeast Saccharomyces cerevisiae is composed of the eight subunits Ost1,
Ost2, Ost4, Ost5, Stt3, Swp1, Wbp1 and, either Ost3 or Ost6. Thereby, two isoforms of the yeast OST
complex exist which are defined by the presence of either Ost3 or Ost6. The aim of this project is to
characterize the yeast OST complex biochemically and structurally to further understand N‐
glycosylation by an oligomeric OST. To purify the OST complex, one of the eight OST subunits will be
tagged in strains expressing only one isoform of OST. Glycosylation efficiency and complex stability will
be analyzed in vivo to screen for the most functional tagged OST complex to be purified. OST enzyme
activity and substrate selectivity will be investigated through in vitro glycosylation assays using
chemically synthesized LLOs and fluorescently labeled peptides as substrates. Finally, structural studies
will be done by cryo‐electron microscopy.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
25
Glycoengineering in insect cells to produce carbohydrate‐based vaccines against Haemonchus contortus
Susanna Fleurkens1, 2, Chia‐Wei Lin1, Alex Butschi2, Bruno Oesch2, Markus Aebi1
1Institute of Microbiology of ETH Zürich, Switzerland; 2Malcisbo AG, Schlieren, Switzerland
The blood sucking stomach worm of sheep Haemonchus contortus causes major economic damage
reducing meat and wool quality. The parasite is currently controlled by chemical treatments yet the
advent of resistant strains necessitates new strategies such as an effective vaccine. It is well known
that glycoprotein‐enriched extracts of adult H. contortus are able to confer immunity thereby reducing
the worm burden. However, attempts to make a recombinant vaccine have failed up to now which
might be due to the lack of glycosylation.
We therefore manipulate the insect N‐glycosylation pathway by overexpressing additional
glycosyltransferases enabling the production of various antigens of H. contortus carrying parasite
specific glycan structures. Here we report the results of the co‐expression of the major antigen H11
and the nematode‐specific galactosyltransferase using High five insect cells. A novel mass
spectrometry analysis tool for identification of site‐specific N‐glycosylation reveals comparable
glycosylation patterns for H11 expressed in “glyco‐modified” insect cells and native H11 extracted from
adult worms. This indicates that we have been able to produce a potential immunogen for a H.
contortus vaccine in large quantities in order to test the hypothesis of the importance of glycosylation.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
26
Characterization of Mycobacterium smegmatis PafBC
Begonia Fudrini, Sibylle Burger, Frank Imkamp
University of Zurich, Institute of Medical Microbiology, Zurich, Switzerland Gloriastrasse 30/32 CH‐8006 Zürich
PafBC is a heterodimeric protein which is encoded by genes that are organized in an operon with the
Pup‐ligase PafA, which is part of the Pup‐proteasome system (PPS) present in mycobacteria and other
actinobacterial species. The PPS is crucial for Mtb resistance towards reactive nitrogen intermediates
(RNI). PafBC however seems to play only a minor role in RNI resistance. PafBC is a heterodimeric
protein and our bioinformatic analysis revealed a helix‐turn‐helix DNA binding motif at the protein’s
C‐termini, implying a function for PafBC as a transcriptional regulator. The current project aims is to
understand the physiological role of PafBC. We therefore generated a pafBC deletion mutant in the
model organism Mycobacterium smegmatis. We will perform a comprehensive analysis of the mutant
under various growth conditions in order to gain initial insights regarding the function of PafBC.
Furthermore, we will conduct iTRAQ analyses in order to detect PafBC dependent proteome changes,
which will provide important information about PafBC regulated pathways.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
27
Correlative Multi‐Modal Imaging for 3D Spheroid Analyses Fanny Georgi, Vardan Andriasyan, Artur Yakimovich, Urs Greber University of Zurich, Institute of Molecular Life Sciences, Winterthurerstrasse 190, 8057 Zürich [email protected] Spheroids are self‐assembled 3‐dimensional (3D) spherical cell aggregates. They are in vitro micro‐scale
tissue mimetics, and can be used for exploring physiological features of healthy or cancerous tissue.
They provide biological complexity and have been shown to be superior assay platforms compared to
monolayer cell culture systems. Moreover, novel techniques allow cultivation of multiple cell types as
spheroids of defined sizes suitable for high‐throughput screening (HTS) assays. Spheroid‐based assays
are used for drug discovery and can be exploited for therapeutic strategies employing oncolytic viruses.
The cellular processes underlying spheroid formation and growth are poorly understood. In addition,
current spheroid‐based HTS assays are largely based on cell population measurements, and therefore
ignore spheroid system complexity. Here, we aim to provide spatial information on molecular markers
and other biological features concealed in spheroid HTS assays to improve accuracy and reliability of
spheroid‐based screens. We present a correlative multi‐modal imaging approach enabling hit
refinements and characterization of molecular properties of a spheroid. We propose live high‐
throughput transmission light imaging as a HTS assay for monitoring spheroid assembly, maturation,
viability and growth. This assay is complemented by a quantification framework characterizing
spheroids using morphological and textural features. Assay endpoints are further characterized in
chemically fixed spheroids employing lightsheet microscopy to 3D‐render spheroids tomograms. We
show that the combination of these modalities is feasible in a correlative funnel‐like manner, which
may allow precise HTS hit refinement. We further show applicability of this approach to study infection
of carcinotypic spheroids by an oncolytic human adenovirus.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
28
The influence of Alzheimer’s Disease‐like amyloid pathology on the immune surveillance in the brain
Christoph Gericke, Claudia Späni, Nora Schweizer, Mario Merlini, Tobias Suter, Luka Kulic, Roger M. Nitsch, Maria Teresa Ferretti
Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich
Objectives. Chronic brain inflammation is a hallmark of Alzheimer’s disease (AD); however, no
protective autoimmunity against amyloid beta peptide (Abeta) is observed so far. Here, we test the
hypothesis that Abeta alters the brain immune surveillance.
Methods. Antigen presenting cell (APC) and T cell numbers and phenotype were studied using ex vivo
analysis via flow cytometry and confocal microscopy. Results from aged transgenic (tg) mouse models
over‐expressing amyloid precursor protein were compared with non‐tg, age‐matched littermates.
Results. In SweArc‐tg mice we have observed reduced major histocompatibility class II (MHC‐II) surface
expression on APCs. Further analysis has revealed that most MHC‐II accumulated intracellularly,
suggesting an immature APC phenotype. Furthermore, we found a significant increase in brain CD8+ T
cell numbers with low effector cytokine production. We could confirm the altered MHC‐II expression
in brain APCs from a second model, the APP‐PS1deltaE9. T cells here comprised less pro‐inflammatory
cells secreting cytokines such as IFNγ or TNFα. No differences were observed neither in APC from
cerebellum nor splenic T cells in transgenic and control animals, indicating a cerebrum and amyloid‐
specific effect.
Conclusions. Our preliminary results suggest that amyloid accumulation in the brain is accompanied
by significant alterations in both MHC‐II expression and T cell cytokine production. Further studies
using both basic in vitro and in vivo approaches are underway to explore the possibility that brain
immune surveillance is defective in the context of AD‐like amyloid pathology.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
29
Signaling in the General Stress Response of Sphingomonas melonis Fr1
Lisa Gottschlich, Sebastian Dintner, Julia Vorholt
Institute of Microbiology, ETH Zürich, Vladimir‐Prelog‐Weg 1‐5/10, 8093 Zürich, Switzerland
lisa‐[email protected]
The phyllosphere represents a harsh environment characterized by constantly changing conditions.
Colonizing bacteria are able to counteract different stress stimuli with a specific as well as a so called
general stress response (GSR). The latter leads to cross‐protection against a variety of different
stresses. In Alphaproteobacteria, the PhyR‐NepR‐σecfG cascade is the central mechanism of GSR. A
stress stimulus sensed by different histidine kinases leads to phosphorylation of the anti‐sigma factor
antagonist PhyR. After subsequent conformational changes, PhyR forms a complex with the anti‐sigma
factor NepR. Therefore, the previously bound alternative extracytoplasmic function sigma factor (ECF)
is released and able to bind RNA polymerase, which leads to differential gene expression. This
conserved partner switching mechanism is also called "mimicry effect".
The aim of this project is to achieve further understanding of GSR in Sphingomonas melonis Fr1, a
gram‐negative, epiphytic Alphaproteobacterium. It is of great interest to gain insight into stress
induced changes of the transcriptome. Therefore, next generation sequencing will be used to compare
mRNA levels of knockout mutants with impaired GSR compared to wildtype under different stress
conditions. Furthermore, the question will be addressed, if there is a "general stress memory" meaning
a dependency of GSR on duration or frequency of stress exposure. It is also essential to analyze the
mode of action of the single domain response regulator SdrG, which has been found to be a positive
regulator of GSR, in order to obtain a more complete picture of that complex signal transduction
pathway.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
30
Dynamic 13C labeling reveals in vivo half‐life of organic coenzymes in exponentially growing cells
Hartl Johannes, Meyer Fabian, Kiefer Patrick & Vorholt Julia
ETH Zürich, Department of Microbiology, Vladimir‐Prelog‐Weg 1‐10/5, 8093 Zürich, Switzerland
A typical cell mainly consists of proteins, nucleic acids, lipids, and to a large proportion, small molecules
(i.e. metabolites). If not acquired from the environment, these constituents are constantly synthesized
and turned over in order to suit both the anabolic and catabolic demand of growing cells.
The turnover of macromolecules has recently received considerable attention, and it has been shown
that proteins can be stable for several generations in microorganisms. In contrast, metabolite pools
typically exchange within seconds. Major factors limiting the half‐life of metabolites are their rapid
consumption, degradation pathways, chemical reactivity and instability, or loss into extracellular
space. Instead, few of these aspects hold for organic coenzymes. They are often end‐point reactions
of biochemical pathways; act as catalysts, and are rarely consumed. Indeed, it has been shown that
some organic coenzymes can be surprisingly long‐lived.
Here, we employed high resolution mass spectrometry and 13C dynamic labeling experiments to
investigate the in vivo half‐life of organic coenzymes in the model organisms E. coli, B. subtilis and S.
cerevisiae. We were able to detect and quantify the intracellular fractional labeling of eight organic
coenzymes, and find that most have a half‐life that is very close to the doubling time of the respective
microorganism. Even after more than three generations, we were still able to detect coenzymes in
which no carbon exchange had occurred. Taken together, our data suggests that despite their
reactivity, most coenzymes are in vivo stable enough to allow carbon exchange close to the minimal
necessary rate, de‐novo synthesis mainly counters dilution by cell proliferation, and
salvage/degradation only plays a minor role.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
31
Hunt for somatic mutations in Linear Localized Scleroderma
Rebecca Higgins1,2, Martin Theiler1,2, Alexandra Smith1,2, Regula Wälchli1,2, Lisa Weibel1,2 and Alexander A. Navarini1
1Department of Dermatology, University Hospital Zurich; 2Department of Dermatology, University Children’s Hospital Zurich.
Linear localized scleroderma (LLS) is a rare connective tissue disorder characterized by chronic
inflammation and accumulation of collagen. This then results in both hardening and thickening of the
skin leading to the affected areas to cave in from atrophy. It can affect patients in areas throughout
the body including arms, legs and in more rare cases the face. This leads to terrible disfigurement that
cannot be concealed. The disease is limited in treatment options and most often these treatments are
unsatisfactory. The incidence of localized scleroderma in adults and children is 2.7/100’000 population
per year classifying it as a rare disease. LLS is characterized by sharply delimited and linear plaques that
are oriented along embryonal cellular migration routes. This suggests that LLS could be caused by a de
novo somatic mutation(s) resulting in a mosaic state as has been described previously in other skin
conditions. The aim of this project is to use whole exome sequencing to find the causative mutation(s).
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
32
From protein function to supermolecular structure: Listeria phage A511 baseplate structure and identification of receptor binding proteins
Mario Hupfeld1, Ricardo Guerrero‐Ferreira2 , Martin Loessner1, Takashi Ishikawa3, Petr Leiman2 and Jochen Klumpp1
1Institute of Food, Nutrition and Health Schmelzbergstrasse 7, ETH Zurich, 8092 Zurich, Switzerland; 2Institut de Physique des Systèmes Biologiques, EPF Lausanne, LBBS, Lausanne, Switzerland ; 3Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen PSI, Switzerland
Our understanding of the infection of Gram‐positive bacteria by phages is still incomplete.
Bacteriophage A511 is a contractile‐tailed, dsDNA, Myoviridae phage with a wide host range within the
genus Listeria. It has been shown to be a good tool in pathogen detection especially in food products.
The first steps in the infection cycle are initiated by the attachment to the surface of the bacterium.
This is believed to be a two‐step process, mediated by two different receptor binding proteins (RBPs).
We could identify one RBP, namely Gp108, supposedly a short tail fibre protein of the phage. Here we
show the results of GFP binding assays carried out for the other protein candidates that come into
contact with the bacterial cell surface upon infection. These include Gp98 and Gp99 which form the
central hub‐like structure of the baseplate. Gp104 is similar to a putative tail fiber, although a function
is not known. Gp106 represents a VrlC like protein, which has been found in a number of phages
infecting both Gram‐positive and Gram‐negative bacteria and is considered a potential receptor
binding protein of phage A511. Future experiments are aimed to further characterize these proteins.
We are also developing a structural model of the A511 baseplate (in the contracted and non‐
contracted state) which will be based on Cryo‐electron microscopy images fitted with crystallized
protein structures. The expected results will elucidate the mechanisms involved in phage contraction,
adsorption and subsequent viral DNA injection.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
33
Dynamics of the bone‐marrow microenvironment during viral infections
Stephan Isringhausen, Nike Kraeutler, Diana Stoycheva, Ute Suessbier, Markus Manz, Annette Oxenius, Cesar Nombela‐Arrieta
Experimental Hematology, University of Zurich, Zurich
Hematopoiesis, the primary function of the bone‐marrow (BM), is a highly dynamic and tightly
regulated process resulting in the production of millions of blood cells per minute under homeostatic
conditions. Continuous hematopoietic cell production is sustained by a rare population of self‐
renewing, multipotent hematopoietic stem and progenitor cells (HSPCs), which reside in specialized
nurturing microenvironments within BM cavities. The BM ecosystem is extremely diverse, comprising
all hematopoietic lineages as well as complex stromal cellular networks of mesenchymal, neural and
vascular origin. Beyond providing a structural scaffold for hematopoietic cells, stromal cells are
critically involved in the fine regulation of different stages of hematopoiesis. Yet, the functional
interplay of stromal components with hematopoietic cells during both homeostasis, as well as in
inflammatory conditions is still incompletely understood.
Bacterial and viral infections trigger major stress in the hematopoietic system inducing an adaptative
response in cellular output. Surprisingly, little is known about the potential damage that potent
inflammatory stimuli can inflict on the BM stroma, resulting in long term dysfunctional hematopoiesis.
Here we combine established in vitro and in vivo assays with cutting‐edge 3D imaging technologies
recently established in our lab, to study the effect of acute and chronic viral infections in the
microarchitectural and functional integrity of the BM.
Our results indicate that viral infections result in rapid vasodilation of BM sinusoids, loss of extracellular
matrix networks and regional emergence of adipocytes. Notably, chronic infections with LCMV clone‐
13 and docile strains induce a profound and sustained reduction in the number of HSCs, which
correlate with a downsizing of the population of mesenchymal stromal progenitor cells and a decrease
in their capacity to produce HSPC‐sustaining factors such as CXCL12. We are currently investigating the
precise molecular and cellular mechanisms driving viral‐induced BM tissue damage.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
34
Conformational protection of antibody epitopes on native HIV‐1 envelope glycoprotein trimers
Branislav Ivan1, Carsten Magnus1, Oliver F. Brandenberg1, Roland Regoes2, Peter Rusert1, Alexandra Trkola1.
1Institute of Medical Virology, University of Zurich, Switzerland; 2Institute of Integrative Biology, ETH Zurich, Switzerland
Antibodies binding non‐native forms of the HIV‐1 envelope glycoprotein (Env) appear early in infection
and are also routinely elicited in animal and human vaccination trials. However, such antibodies fail to
bind the functional Env trimer and to neutralize most HIV‐1 isolates. A major driver of antibody
resistance of the Env trimer is the V1V2 domain of gp120 which shields neutralization sensitive
epitopes of gp120, in particular the V3 loop. Two modes of V3 loop shielding by the V1V2 loop have
been proposed: I) self‐protection where both V3 and V1V2 are located on the same protomer within
the Env trimer and II) neighboring‐protection where the V1V2 loop from one protomer shields the V3
loop on the neighboring protomer. Thus far structural and functional studies of the HIV‐1 envelope
yielded inconclusive or even seemingly contradicting results concerning the mode of V3 protection by
the V1V2 loop raising the possibility that both protection modes may occur depending on the envelope
and epitope studied.
To probe this, we tested the binding of a range of V3 directed antibodies and inhibitors to envelope
proteins from divergent HIV strains in the context of mixed HIV Env trimers containing antibody binding
sensitive or resistant V3 loops in presence or absence of the V1V2 loop. Employing a mathematical
model we previously described that predicts antibody binding to mixed trimers allows us to assess the
stability of mixed trimers and dissect the mode of V1V2 loop protection.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
35
Response to nitrogen limitation in Burkholderia phymatum and competition between β‐rhizobia for legumes infection
Martina Lardi1, Gabriela Purtschert1, Maria Sanchez‐Contreras1, Alessandro Pedrioli1, Yilei Liu1, Christian Ahrens2, Leo Eberl1 and Gabriella Pessi1
1Institute of Plant Biology, Department of Microbiology, UZH Zurich, Switzerland; 2Institute for Plant Production Sciences, Agroscope, Wädenswil, Switzerland
Rhizobium‐legume symbiosis is of major ecological and economic importance and accounts for two‐
thirds of the nitrogen fixed globally. Until recently, all known examples of symbiotic relationships
between legumes and prokaryotes were confined to the phylogenetically diverse α‐rhizobia. This
changed with the discovery of certain β‐proteobacteria of the genera Cupriavidus and Burkholderia,
which are also capable of establishing nitrogen‐fixing symbiosis with legumes. At present, very little is
known about molecular determinants underlying the successful establishment of the symbiosis
between legumes and β‐rhizobia.
In rhizosphere, rhizobia are subject to changing environmental conditions, including nutritional
stresses. It has been shown that under nitrogen limited conditions β‐rhizobial strains such as
Burkholderia phymatum STM815 are the most competitive symbionts.
In this study, we used RNA‐Sequencing to investigate the transcriptome of B. phymatum in response
to nitrogen limitation. Among the genes responding significantly to nitrogen limitation, we found
several genes for nitrogen assimilation. In addition we found also genes coding for proteins involved
in polyhydroxybutyrate accumulation as well as exopolysaccharide synthesis. We next investigated the
capacity of seven β‐rhizobial strains to compete for nodulation of different legumes. We found B.
phymatum to be the most competitive strain on Vigna unguiculata, and Burkholderia tuberum was the
most successful strain on Macroptilium atropurpureum. Phaseolus vulgaris was found to be
preferentially nodulated by B. tuberum and B. phymatum. While Mimosa pudica was nodulated by B.
phymatum and Burkholderia mimosarum. The identification of genes important for competiveness
would allow us to better understand natural selection for high nitrogen fixation capacity.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
36
Infection‐induced changes in regulatory T cells
Katharina Littringer & Nicole Joller
Institute of Experimental Immunology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland
CD4+ Foxp3+ regulatory T cells comprise a highly heterogeneous population of immune modulatory
cells essential for maintaining immune homeostasis. In the course of infections Tregs differentiate into
phenotypically and functionally diverse subsets, parallel to effector T helper (Th) cell responses.
Activated Tregs mirror their Th‐counterparts in their expression of lineage specific transcription factors
such as Tbet (Th1), IRF4 (Th2) or Stat3 (Th17) as well as specific chemokine receptors. This
specialization seems to enable selective control of ongoing immune responses and Treg recruitment
to the site of inflammation. Nevertheless, how the Treg compartment is altered by infections triggering
distinct types of Th responses is still only poorly understood. Not only the nature of Tregs (natural vs.
induced) and their phenotypic changes but especially how their suppressive capacity is affected during
an infectious challenge will be the focus of our work. We address this question in the setting of an
acute infection with Lymphocytic Choriomeningitis Virus (LCMV) or Candida albicans, which generate
a polarized Th1 or Th17 immune response, respectively. Our experiments indicate that Treg activation
in mice, infected with LCMV peaks at day 10 to 14 p.i. Within this timeframe surface receptors and
markers, known to promote Treg specific function, such as CXCR3, CTLA‐4, TIGIT, PD‐1 are highly
upregulated when compared to naïve mice as assessed by flow cytometry. How functionality of this
activated population is changed in those settings will be investigated in a next step using in vitro
suppression assays.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
37
Investigation of factors influencing pC3 stability within the Burkholderia cepacia complex Olga Mannweiler, Dr. K. Agnoli‐Antkowiak and Prof. L. Eberl Department of Microbiology, University of Zürich, Zollikerstr. 107, Switzerland [email protected] The Burkholderia cepacia complex (Bcc) is a group of 18 closely related but metabolically versatile
bacterial species, which are able to occupy a variety of environmental niches. Strains of the Bcc are
known as important, life‐threatening opportunistic pathogens for immunosuppressed patients and
individuals suffering from cystic fibrosis. Bcc members harbour three large replicons of which 2 are
chromosomes carrying essential genes and a nonessential megaplasmid, pC3, associated with
virulence and both antifungal and proteolytic activities. It has been shown that it is possible to delete
pC3 from most Bcc members using a plasmid incompatibility approach. The mobilization of pC3 and
therefore its transfer by conjugation was achieved, but this was only possible between certain Bcc
members.
The objective of this project is to investigate the factors that may cause the transfer difficulties
between the Bcc strains by phenotypical, biochemical and functional genomics analyses. Our current
hypothesis is that this might be due to the effect of restriction‐modification (RM) systems. Rebase ®,
the restriction enzyme database, shows that there is a variety in the RM systems for all sequenced
members of the Bcc. Sequencing of the Bcc strains by using the PacBio SMRT technology and
determining the methylome will allow us to compare their methylation patterns, giving us an indication
of how to improve pC3 transfer. Another approach refers to the presence of potential contact‐
dependent growth inhibition systems and whether they affect the pC3 transfer. To test this possibility,
competition assays will be performed
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
38
Glyco‐conjugate vaccine against Dirofilaria immitis
Francesca Martini1, 2, Chia‐wei Lin2, Alex Butschi1, Bruno Oesch1, Markus Aebi2
1Malcisbo AG, Schlieren, Switzerland; 2Institute of Microbiology of ETH Zürich, Switzerland
Dirofilaria immitis is a parasitic nematode of canidae and the primary cause of cardiopulmonary
dirofilariosis in dogs, cats and ferrets, presenting also zoonotic potential. This parasite is currently
controlled by chemical treatments which prevent the infection. The preventive treatment presents
several disadvantages, the drugs are highly toxic for the dogs and very expensive. Furthermore, in
recent years several cases of anthelmintic resistances have been reported, which indicates the need
for new strategies to control this infection. The goal of this project is to develop the basis for a novel
vaccine against the blood‐sucking nematode Dirofilaria immitis in dogs. To date, no potential vaccine
targets have been found in D. immitis. However, several promising vaccine candidates of other blood
sucking nematodes have been published, for example of Ancylostoma caninum, the dog’s hookworm.
Searching the D. immitis genome for homologous A. caninum antigens might therefore be a valuable
strategy for vaccine target identification. Moreover, in recent years it has become evident that the
protein backbone of an antigen is not the only factor eliciting a protective immune response, also
secondary structure and post‐translational modifications, like glycosylation, are to be taken into
account. Thereby our strategy comprises the use of Mass Spectrometry analysis and lectin blotting to
gain information about the glycome of D. immitis at various developmental stages that will be used to
generate a glyco‐conjugate vaccine.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
39
N‐linked glycosylation in the Endoplasmatic Reticulum and Golgi
Corina Mathew
Institute of Microbiology, ETH Zurich, HCI, Wolfgang‐Pauli‐Strasse 10/Vladimir‐Prelog‐Weg 4 CH‐8093 Zurich, Switzerland
The N‐linked glycosylation of proteins is one of the most prevalent post‐translational modifications
and ubiquitous among all kingdoms of life. Attached to a protein, N‐glycans contribute to a variety of
biological functions: They are for example crucial for protein folding, contribute to the quality control
that takes place in the endoplasmatic reticulum (ER) and alter the behavior of a protein regarding
protein stability, solubility, immune response and cellular function. These properties make the study
of the N‐glycosylation process of proteins an important task, because not only academics but also the
production of pharmacological relevant glycoproteins could benefit from the generated knowledge.
The complex biosynthesis of glycoproteins includes assembly of an oligosaccharide recursor, transfer
of the precursor onto nascent polypeptide chains, and modification of the glycan in the ER and the
Golgi. The great diversity of glycans observed on secreted proteins is species‐, tissue‐ and cell‐specific
and produced in the Golgi. Here a variety of glycosyltransferases and glycosidases process the initial
sugars. Our group previously showed that the protein structure and its interaction with the covalently
attached glycans are the major determinants of N‐glycan processing. To study the importance of
glycan‐protein interactions we will employ a number of different in vivo and in vitro experiments along
with in slico techniques to further test and develop these findings. Amino acid residues that showed
prolonged interaction with the glycans of the model protein in molecular dynamic studies will be
mutated to test whether these mutations alter N‐glycan profiles on the respective site. If time allows,
we will start to reconstitute in vitro selected glycosylation steps.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
40
Identification of a Novel Genetic Cause of Hypereosinophilia
Andrea Mauracher, Jana Pachlopnik, Stefano Vavassori, Lennart Opiz
UZH, Kinderspital Zürich, Pädiatrische Immunologie, August‐Forel Strasse 7, 8008 Zürich
Eosinophils play an important role in the pathophysiology of allergic, parasitic and malignant diseases
and normally only 1‐3% of all peripheral leukocytes are eosinophils. Eosinophils can infiltrate tissues
and cause extensive tissue damage. They can also secrete cytokines that can activate the adaptive
immunity and can act as antigen presenting cells. The proliferation and differentiation of eosinophils,
their survival in the blood and tissue as well as their localization is stimulated by cytokines and growth
factors including IL‐3, granulocyte macrophage colony‐stimulating factor (GM‐CSF), and IL‐5. Activated
T‐cells are believed to be the main producers of these cytokines whereby IL‐5 is the cytokine most
specific for eosinophils. In contrast, IL‐3 and GM‐CSF exhibit more pleiotropic functions.
Understanding the factors that regulate eosinophils is pivotal in developing new therapeutic
approaches. There still are many mysteries in patients presenting Hypereosinophilia and they offer a
good starting point to unravel the functionality of eosinophils further.
We are analysing two patients who both have a very unique phenotype that we believe could provide
further insights into the aetiology of hypereosinophilia. Our hypothesis is that the hypereosinophilias
seen in our patients are due to a novel genetic mutation. Our aim is to identify the mutations and
establish the link between the mutations and the hypereosinophilia by the use of whole exome
sequencing as well as various in vitro methods.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
41
Molecular Epidemiology of Transmitted HIV‐1 Drug Resistance in Drug‐Naive and Newly Diagnosed Patients in Cameroon
Herbert A. Mbunkah, Stefan Schmutz, Alex Marzel, Nottania K. Campbell, Roger Kouyos, Günthard Huldrych, Karin J Metzner
Institute address: University Hospital Zurich, Division of Infectious Diseases and Hospital Epidemiology, Rämistrasse 100, CH‐8091 Zurich
The use of combinations of antiretroviral drugs has proven remarkably effective in controlling the
progression of HIV‐1 and prolonging survival, but these benefits can be compromised by the
development of drug resistance. There is very limited data on HIV‐1 drug resistance mutations in our
study site (Cameroon). We plan to determine the prevalence, types and transmission patterns of
resistance‐associated mutations in drug‐naive and newly diagnosed HIV‐1 patients in Cameroon. At
least 300 blood samples will be collected within a period of one year from some hospitals running HIV
treatment centres in Cameroon. Dried blood spot samples will be collected and stored for onward
transmission to Switzerland. For genotype resistance testing, the next‐generation sequencing (NGS)
platform Illumina MiSeq will be used to sequence the protease and reverse transcriptase genes of HIV‐
1 in these clinical samples. A NGS assay suitable for all subtypes will be scaled up to develop an
affordable drug resistance assay which might be suitable for drug resistance testing in resource limited
countries. The assessment of transmitted resistance will be done as described by the International
AIDS Society‐USA (IAS‐USA) and by the list of drug resistance mutations for surveillance of transmitted
HIV‐1 drug resistance, recommended by the World Health Organization (WHO). Phylogenetic trees will
be constructed with Clustal W, using reference pol sequences. Routine baseline information on the
frequency and types of drug resistance mutations in Cameroon will help to inform optimal
antiretroviral therapy and enable the government to better monitor the success of the national AIDS
treatment program.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
42
Methylotrophy ‐ From understanding to engineering
Fabian Meyer, Jonas Müller, Patrick Kiefer, Julia Vorholt
Institute of Microbiology, ETH Zurich, Vladimir‐Prelog Weg 4, 8093 Zürich, Switzerland
The ability to use methanol as sole carbon source makes methylotrophs interesting candidates for
industrial applications. The potential of natural methylotrophs such as Bacillus methanolicus has so far
been restricted, due to the lack of tools for genetic manipulation. As an alternative approach this study
has the aim to combine the potential of a methanol based metabolism with the genetic accessibility of
Escherichia coli by engineering a methylotrophic E. coli using synthetic biology. Achieving this goal is
combined with a deep understanding of the system biological properties of natural methylotrophs.
Performing metabolome analysis in the natural methylotroph B. methanolicus might help to identify
methylotrophic specific features needed to create an artificial methanol utilizing E. coli. So far we
managed to create an engineered E. coli strain which is able to significantly incorporate methanol into
different core‐metabolites, up to 40% in case of hexose‐6‐phosphate. The incorporation of methanol
was shown by using dynamic 13C labeling experiments starting from 13C methanol.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
43
Fluidic Force Microscopy ‐ A Novel Technology for Single‐Cell Manipulation and Micropatterning
Maximilian C.A. Mittelviefhaus1, Eva Potthoff1, Orane Guillaume‐Gentil1, Tomaso Zambelli2, Julia A. Vorholt1
1ETH Zurich, Institute of Microbiology, Vladimir Prelog Weg 4, CH‐8093 Zurich; 2ETH Zurich, Institute for Biomedical Engineering, Gloriastrasse 35, CH‐8092 Zurich [email protected]
There is increasing interest to manipulate and analyze single cells, e.g. to uncover cell‐cell interactions
or to investigate single cell behavior in complex consortia in a time and space dependent manner.
Fluidic force microscopy (FluidFM) is a recently invented technology that addresses the demand for
novel single‐cell research. By combining atomic force microscopy with microchanneled cantilevers and
microfluidics, FluidFM constitutes a unique technique for local fluid delivery, lithography, single‐cell
manipulation, and micropatterning.
The microchannels in the cantilever form a continuous fluidic circuit between an externally connected
pressure controller and an aperture in the tip of the cantilever. Application of overpressure or vacuum
allows controlled manipulation of liquids within the cantilever. Overpressure, for example, can be
utilized for controlled liquid injection after cell penetration into single cells. By creating a vacuum,
micro‐objects, including single bacterial cells, can reversibly be immobilized on the cantilever and be
used for precise measurements of adhesion forces in a serial manner. By exploiting both, vacuum and
overpressure application, the system allows for pick‐and‐place experiments of single cells. By defined
spatial manipulation of individual bacteria, FluidFM can also be used to create arrangements of
microorganisms to investigate cell‐cell interactions in a time and space dependent manner.
Furthermore, the technology can be used as versatile lithography tool through force and pressure
controlled local polymer delivery. Adhesive surface coatings within a nonfouling background, such as
poly‐L‐lysine (PLL) on a PLL‐g‐poly‐ethylene‐glycol (PEG) background, enable the immobilization of
bacteria and the systematic study of cell‐cell interactions at defined distances.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
44
An in vivo study of HIV virus distribution and HIV‐Env specific antibodies in order to eliminate
latently infected cells
Christina Müller
University Hospital Zürich, Rämistrasse 100, 8091 Zürich
Combined antiretroviral therapy (cART) is the current state of the art in treating HIV. cART achieves in
most patients a long‐term suppression of HIV and has a remarkable positive impact on morbidity and
mortality. However, HIV rebounds after interruption of therapy. This rebound is due to long‐lived
latent HIV‐infected CD4+ cells and is one of the major hurdles in eliminating HIV infection. In addition,
the viral diversity of HIV resulting in immune and drug escapes as well as the lack of a vaccine are major
barriers towards finding a cure for HIV. Nevertheless, over the past years, new promising potent and
broadly neutralizing antibodies targeting the HIV envelope (HIV‐Env) have been identified and isolated.
These antibodies could provide a tool to eventually eliminate HIV. Therefore it is important to
investigate the specificities of the antibodies regarding to their ability to control HIV infection in vivo.
Furthermore these antibodies can be used to achieve a better understanding of HIV latency in vivo.
To investigate these two aspects in vivo the humanized mice model provides a good tool and therefore
will be used in this context. The goal is to evaluate the most effective antibodies for therapy. Therefore
HIV‐Env specific antibodies targeting different epitopes will be tested in HIV infected humanized mice.
Furthermore it is the aim to use labeled HIV‐Env specific antibodies in order to follow the virus
distribution during progression of disease by in vivo imaging. Finally, we will study combinations of the
most efficient HIV‐specific antibodies in concert with compounds activating latently infected cells for
their efficient elimination.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
45
Anti‐TNF promotes type I interferon‐driven psoriasis‐like skin inflammation
Curdin Conrad1, Jeremy Di Domizio1, Alessio Mylonas1, Cyrine Belkhouja1, Olivier Demaria1, Anne‐Karine Lapointe1, Maxime Vernez1, Alexander Navarini2, Lars French2, Michel Gilliet1
1Departement of Dermatology, CHUV Lausanne; 2Departement of Dermatology, University Hospital of Zurich
Email: [email protected]
Paradoxical psoriasis is a well‐known side‐effect of anti‐TNF therapy affecting 2‐5% of treated patients.
As this side effect often necessitates cessation of the anti‐TNF therapy, there is an urgent need to
understand its pathogenesis. Here, we analyzed a series of 25 cases of paradoxical psoriasis induced
by all anti‐TNF agents available. Underlying diseases, clinical presentation and histological patterns
varied considerably among patients. However, we found a striking, uniform, and selective upregulation
of type I interferons (IFN) in skin of paradoxical psoriasis as compared to classical psoriasis. The
overexpression of type I IFN was paralleled by a massive accumulation of plasmacytoid dendritic cells
(pDCs) within the skin. In‐vitro, TNF blockade directly enhanced type I IFN production by pDCs, while
TNF itself inhibited its production suggesting a crossregulation of TNF and pDC‐derived type I IFN. In a
skin injury mouse model, anti‐TNF therapy increased and sustained type I IFN expression and skin
infiltration by pDCs and was sufficient to induce a psoriatic phenotype in a type I IFN‐dependent
manner. Our study demonstrates that anti‐TNF therapy unleashes unabated type I IFN production by
pDCs, thereby inducing a psoriasis‐like skin phenotype. Thus, we unravel the pathomechanism of
paradoxical psoriasis and provide a clinical relevance for the crossregulation of TNF and type I
interferon.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
46
Infection‐Induced Alterations of CD4+ T Cell Responses upon Heterologous Challenge
Nikolas Rakebrandt & Nicole Joller
University of Zürich, Institute of Experimental Immunology, Winterthurer Strasse 190
CD4+ Foxp3+ regulatory T cells (Tregs) are essential in maintaining self‐tolerance. Recent evidence
suggests that they also play a crucial role in modulating the nature of the immune response. Depending
on the challenge, CD4+ effector T cells differentiate into specialized T helper (Th) lineages such as Th1,
Th2 and Th17, which are defined by production of distinct sets of cytokines. In order to cope with the
diversity of CD4+ T cell responses, Tregs show a similar level of heterogeneity and thereby the capacity
to regulate the entire range of effector responses. Emerging evidence suggests the formation of tissue
resident memory Tregs following immune responses. However, whether memory‐dependent changes
in the composition of the Treg compartment affect the nature of secondary challenges is still unclear.
We aim to analyze if a preceding acute infection affects the type or magnitude of the immune response
upon heterologous challenge and whether this is dependent on an altered Treg compartment or
formation of regulatory memory. To address this question, mice are primed with acute lymphocytic
choriomeningitis virus (LCMV), which induces a Th1 response and then challenged, after viral
clearance, with Legionella pneumophila eliciting a mixed Th1/Th17 cell response. We then analyze the
effector CD4+ T cell response and Treg populations using flow cytometry. Overall, these experiments
will allow us to assess if a preceding immune response alters the nature of the immune response upon
heterologous challenge and how this affects susceptibility to pathogenic challenges or autoimmune
diseases.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
47
Impact of Nlrp3 x gut microbiota interactions on experimental colitis and insulin sensitivity
Felix Rost1, P. Pavlov1, S. Wueest2, K. Atrott1, G. Rogler1,3, D. Konrad2,3, I. Frey‐Wagner1,3
1Division of Gastroenterology and Hepatology, University Hospital Zurich, Raemistrasse 100, CH‐8091
Zurich, Switzerland; 2Division of Endocrinology and Diabetology, University Children’s Hospital Zurich,
Steinwiesstrasse 75, CH‐8032 Zurich Zurich, Switzerland; 3Zurich Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, CH‐
8057 Zurich, Switzerland
Introduction: NOD‐like receptor pyrin domain containing 3 (Nlrp3) genotype has been shown to affect
murine experimental colitis and glucose metabolism. We here investigate whether Nlrp3 genotype‐
induced changes in gut microbiota composition are involved in the observed effects.
Methods: Female Nlrp3‐/‐ and wild‐type (WT) littermates underwent dextran sodium sulphate (DSS)‐
induced acute (7 days, 1% DSS) or chronic colitis (4 x 7 days, 1% DSS). Colitis severity was evaluated by
inflammatory parameters. Male Nlrp3‐/‐ and WT littermates received a high fat diet (HFD) or normal
chow for 6 weeks and glucose tolerance was assessed. Gut microbiota composition was studied by 16S
rRNA amplicon sequencing before and after induction of colitis / HFD.
Results: Nlrp3‐/‐ mice showed a more severe phenotype in acute and chronic DSS colitis. HFD‐fed
Nlrp3‐/‐ mice showed slightly improved glucose tolerance compared to WT littermates. Notably, Nlrp3‐
/‐ and corresponding WT littermates differed strongly in their gut microbiota composition under basal
conditions as well as after induction of colitis.
Discussion / Outlook: Gut microbiota composition, experimental colitis and glucose tolerance are
affected by the Nlrp3‐/‐ genotype. Further experiments with microbiota transfer between genotypes,
and colitis models / HFD experiments in animals with a limited defined flora will address a causal
relationship between gut microbiota composition and colitis / glucose tolerance outcome. Samples of
the Swiss IBD cohort (SIBDC) from patients with NLRP3 polymorphisms will be analyzed to compare
and extend the relevance of our findings to microbiota x genotype interactions in humans.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
48
The role of HDAC6/Ubiquitin/aggresome pathway in the influenza virus infection
Alina Rudnicka, Yohei Yamauchi
University of Zurich, Institute of Molecular Life Sciences, Winterthurerstrasse 190, CH‐8057 Zurich,
Switzerland
All viruses rely on host factors to support their life cycle. Identification and understanding of these
factors can facilitate development of antiviral drugs. Influenza A virus (IAV) is an enveloped single‐
stranded, negative‐sense RNA virus that belongs to the Orthomyxoviridae family. After its endocytic
uptake, infection of IAV depends on uncoating of the genome, protected in the virion by the M1 capsid
shell. Cytoplasmic histone deacetylase 6 (HDAC6) is a host factor that supports IAV capsid disassembly.
HDAC6 contains a zinc‐finger ubiquitin binding (ZnF‐UBP) domain that recognises unanchored
ubiquitin chains, a hallmark of misfolded protein aggregates. By packaging unanchored ubiquitin IAV
mimics a protein aggregate and hijacks HDAC6 to connect the capsid to motor proteins.
The goal of the project is to determine how HDAC6/Ubiquitin/aggresome pathway promotes IAV entry
and infection. Diverse approaches will be employed to interfere with HDAC6‐ubiquitin binding
followed by the analysis of their effects on IAV entry. First, IAV entry in MEF WT and HDAC6 KO cell
lines is compared by transmission electron microscopy. Second, we will target the HDAC6 ZnF‐UBP
domain by expressing nanobodies in A549 (human lung carcinoma) cells, and analyze their effect on
IAV uncoating and infection. Third, a targeted siRNA screen on ubiquitin‐related genes will be
performed in order to identify additional host factors that are necessary for IAV. This project is relevant
for future treatment strategies against viruses that utilize HDAC6 and aggresome processing.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
49
Combining antigen formulations for human vaccination against cancer
Julia Rühl, Carol Leung, Christian Münz
University of Zurich, Institute of Experimental Immunology, Winterthurerstrasse 190, CH‐8057 Zürich
Epstein‐Barr virus (EBV) is a γ‐herpesvirus that preferentially infects B cells and establishes life‐long
chronic infection in more than 90% of the adult human population worldwide. The infection is usually
asymptomatic, and T cell responses clearly play an important role in maintaining the virus‐host
balance. However, when T cell immune control fails, EBV is associated with a number of human
malignancies such as Burkitt’s lymphoma, Hodgkin’s lymphoma and nasopharyngeal carcinoma. All
EBV‐positive tumor cells express the EBV nuclear antigen 1 (EBNA1), therefore EBNA1 is an important
target for protective immunity.
EBV has an exclusive tropism for humans, therefore the studied model organism is NOD‐‐/‐ mice with
human immune system components, which develop in these mice after neonatal intrahepatic injection
of human CD34+ hematopoietic progenitor cells (huNSG mice).
Targeting antigens to dendritic cells (DCs) is a promising strategy for therapeutic vaccinations. DCs are
important for initiating protective innate and adaptive immune responses against pathogens. T cell
responses can be enhanced through antigen delivery to endocytic receptors on DCs. Our group has
previously demonstrated that targeting EBNA1 to DEC‐205 elicits promising Th1‐type CD4+ T cell
responses in vitro and in vivo with a suitable adjuvant. However, targeting EBNA1 to DEC‐205 in vivo
induced poor CD8+ T cell responses. Therefore, we aim to improve the T cell responses by targeting
EBNA1 to different DC specific receptors in combination with other vector‐based delivery such as viral
vectors.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
50
MCMV‐Specific T Cell Immunity in the Salivary Gland
Katharina Schmidt, Jenny Thom, Annette Oxenius
ETH Zurich – Institute of Microbiology, Vladimir‐Prelog‐Weg 4, CH‐8093 Zurich, Switzerland
Cytomegaloviruses (CMVs) are β‐herpesviruses infecting 60–90% of the human population. Even
though acute CMV infection is mostly asymptomatic in immunocompetent individuals, it can cause
fatal disease in the immunocompromised. Latency of the virus is established in secretory glands, such
as the salivary gland (SG), from where it continuously disseminates via mucosal secretions. Infection
of mice with murine CMV (MCMV) is a commonly used model to study the biology of infection.
MCMV infects many cells types but during established infection it mainly infects and replicates in acinar
glandular epithelial cells (AGECs) for several weeks in the SG. Prolonged infection in the SG is caused
by a failure of CD8+ T cells to control viral replication due to a virus‐mediated interference with
antigen‐presentation in infected AGECs. Therefore, IFNγ‐producing CD4+ T cells are required to
effectively control lytic infection at this site. Our group showed that systemic MCMV infection induces
tissue‐resident memory T cells (TRM) in the SG, either in an antigen‐dependent (CD4+) or –
independent (CD8+) manner. In striking contrast to CD8+ effector T cells during acute infection, we
showed that CD8+ TRM are able to mediate immediate protection against localized MCMV infection
of the SG. Here, we aim to characterize tissue intrinsic and viral factors responsible for the
susceptibility of the SG to MCMV infection. Additionally, we intend to use traceable MCMV‐specific T
cells in combination with GFP‐expressing MCMV to analyze the dynamic behavior of virally infected
cells and virus‐specific T cells in the SG by intravital microscopy.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
51
Sickness behavior syndrome and clock gene disregulation in inflammatory bowel disease
Sellés‐Moreno C., Strauss L. & Fontana A.
Institute of Experimental Immunology, Winterthurerstrasse, 190 Y44 J68 Zürich 8003, Switzerland
Sickness behavior syndrome (SBS) as characterized by fatigue, depression and weight loss impairs
significantly the quality of life of patients with chronic inflammatory diseases. This holds also true for
an experimental model of inflammatory bowel disease (IBD), which is induced in mice with orally
administrated dextran sodium sulphate (DSS). The change of behavior becomes evident by loss of
locomotor activity as well as body weight loss. SBS is associated with altered clock gene expression in
the spleen and colon of mice with DSS colitis. Dysregulated clock gene expression has been shown to
be due to the effect of the
proinflammatory cytokines TNF‐a and IL‐1b.
We hypothesize that inflammation leading to the abnormal clock gene expression observed may
disrupt circadian rhythms resulting in fatigue, depression and metabolic disorders. Our new data show
that TNF and IL‐1β are largely produced by myeloid cells in inflamed tissue and blood. These cytokines
suppress the expression of clock output genes (Cry1 and 2, Per 1, Per2 and Per3 as well as the PAR bZip
transcription factors Dbp, Tef, Hlf) in vivo, and nuclear receptors involved in circadian rhythms
regulation .We find nuclear receptors involved in metabolic sensing are expressed in inflammation‐
activated macrophages and are directly implicated in controlling myeloid precursor commitment and
functional polarization. Preliminary results of our group show that expression patterns of clock and
nuclear receptors in inflamed colon and spleen in DSS‐mediated colitis in mice directly correlate with
body weight loss, disease severity and survival.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
52
Characterization of Legionella effector proteins involved in the modulation of small GTPases
Leoni Swart, & Hubert Hilbi
University of Zürich, Institute of Medical Microbiology, Gloriastrasse 30/32, CH‐8006 Zürich, Switzerland
Legionella pneumophila is a ubiquitous water‐borne bacterium and the causative agent of the
severe pneumonia termed Legionnaires’ disease. The opportunistic pathogen infects lung
macrophages upon inhalation of contaminated aerosols. Once intracellular, the bacterium injects
approximately 300 effector proteins into the host cell via an Icm/Dot type IV secretion system (T4SS).
These proteins manipulate various host cell processes, like protein and vesicular trafficking, and
thereby prevent degradation of the pathogen via the bactericidal endolysosomal pathway. So far, only
a limited number of effectors have been characterized in detail.
Proteomic analysis of purified intact Legionella‐containing vacuoles (LCVs) revealed the presence
of hundreds of host proteins including a number of small GTPases implicated in the secretory and
endosomal vesicle trafficking pathway, as well as Ran and its effector Ran binding protein 1 (RanBP1).
The bacterial effector protein LegG1 has been found to activate Ran and thereby promote LCV
formation and motility, microtubule polymerization and bacterial replication.
Several members of the Rab GTPase family are also targeted by Legionella. Especially Rab1, which
is activated, inactivated and modified by bacterial effector proteins to regulate its function. AnkX has
been identified as a Legionella substrate which phosphocholinates Rab1 and thereby prevents the
inactivation of Rab1, yet also impairs binding downstream effector proteins. Hitherto, the exact
mechanism of action of most effector proteins, including LegG1 and AnkX, remains unknown. This PhD
project focuses on the characterization of LegG1 and its paralogues and orthologues, in particular the
mechanism of Ran activation. In addition, host targets and the phosphocholination mechanism of AnkX
will be investigated.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
53
Caulobacter crescentus cell division is rate‐limited by peptidoglycan remodeling
Seamus Holden, Ambroise Lambert, Aster Vanhecke, Suliana Manley
École Polytechnique Féderale de Lausanne (EPFL), Laboratory of experimental biophysics (LEB), 1015 Lausanne, Switzerland
Bacterial cell division is a fundamental process central to bacterial growth and thus survival, involving
many highly conserved and essential genes. FtsZ is the first protein that is recruited to midcell, where
it forms a ring‐like structure and recruits a collection of proteins, termed the divisome, of which a lot
are involved in the remodeling of the cell wall. Despite meticulous research it is not known how and
to which degree the FtsZ‐ring and cell wall remodeling contribute to constriction. Using super‐
resolution microscopy, we were able to accurately measure the shape of Caulobacter crescentus cells
and thus also the size of the constriction site. High throughput imaging of synchronized cells provided
us with temporal information, which allowed us to measure the rate of constriction. We observe that
constriction, as measured by decrease in diameter, accelerates, such that the amount of newly
produced cell wall per unit time stays constant during constriction. Moreover, perturbations to various
targets involved in septal cell wall remodeling influence the constriction rate. We propose a model
where cell wall remodeling rate determines the rate of constriction.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
54
Role of B cells in human rhinovirus infection
O.F. Wirz1, W. van der Veen1, C. Altunbulakli1, H. Morita1, S.L. Johnston2, N. Glanville2, C.A. Akdis1, and M. Akdis1
1SIAF, University of Zurich, Obere Strasse 22, Davos Platz, Switzerland; 2 Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, United Kingdom
Here, we studied the effect of infections of one major group rhinovirus (HRV 16) and one minor group
rhinovirus (HRV 29) on human immune system cells to investigate their roles in allergy and asthma
exacerbations and chronicity.
When PBMC from allergic and nonallergic individuals were stimulated with different types of HRVs, a
virus dose‐related cellular proliferation was observed, which was particularly confined to the B cell
compartment. We also found that CD19+ B‐cells could be infected by HRV16 and 29 in vitro. We
developed a set of primers to detect positive and negative strand viral RNA of HRV 16 and HRV 29.
While positive strand RNA will be detected from virus which is inside the cell as well as virus attached
to the cell surface, negative strand viral RNA can only be found when virus is in the replication process.
In our experiments, we could detect viral RNA in B cells at different timepoints after infection. Also,
pure B cells were infected with HRV16 and 29 and viral replication was also shown here. We could also
show that proliferating B cells, expressing elevated levels of ICAM‐1 show much smaller viral loads
than non‐proliferating B cells.
Our findings demonstrate for the first time, that human rhinoviruses have the ability to stimulate B
cells and activate plasmablasts. Furthermore, this study delivers the first evidence that B cells can be
infected by human rhinovirus.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
55
HIV‐1 Integration Site Patterns in Monocyte‐derived Macrophages and CD4+ T Cells are “Same Same but Different”
Yik Lim Kok1,2, Valentina Vongrad1,2, Mohaned Shilaih1,2, Francesca D. Giallonardo3, Roger Kouyos1,2, Huldrych F. Günthard1,2, Karin J. Metzner1,2.
1Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland; 2Institute of Medical Virology, University of Zurich, Zurich, Switzerland; 3Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney, Australia.
The host’s genetic landscape surrounding integrated HIV‐1 has an impact on the fate of the provirus,
i.e. productive or latent. Studies analysing HIV‐1 integration sites in CD4+ T cells are numerous but
scarce for macrophages, the other major cellular target of HIV‐1. Here, we characterized HIV‐1
integration site patterns between monocyte‐derived macrophages (MDMs) and activated CD4+ T cells
within the same experimental settings. We analysed a total of 1,484 unique HIV‐1 integration sites
derived from seven ART‐treated HIV‐1‐infected individuals whose MDMs and CD4+ T cells were
isolated and infected ex vivo with autologous primary HIV‐1 isolates and heterologous HIV‐1. HIV‐1
integration site distribution in the human genome, basic host’s genetic requirements for HIV‐1
integration, and nucleotide selection specificity at HIV‐1 integration sites conferred by naturally
occurring amino acid polymorphisms in HIV‐1 integrase (S119P and T122I) were indistinguishable
between MDMs and CD4+ T cells. However, the repertoire of structural and functional HIV‐1 hosting
gene clusters in MDMs was distinct from that of CD4+ T cells. This distinction was further reinforced
by the different frequencies of HIV‐1 integration events in genes encoding HIV‐1 interacting proteins,
as well as frequencies of clonally expanded HIV‐1 hosting genes in gene hotspots between the two cell
types. These data suggest that different shock‐and‐kill strategies may be required to purge the entire
viral reservoir, and clonally expanded HIV‐1 hosting genes may be propagated by factors other than
the functional nature of the targeted genes.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Dissecting the biosynthetic pathway of O‐methylated glycans in Caenorhabditis elegans
Christina Zach, Markus Künzler, Markus Aebi
Vladimir‐Prelog‐Weg 1‐5/10, 8093 Zurich, Switzerland
Multicellular fungi produce cytoplasmic lectins implicated in fungal defense against predators.
Recently Tectonin 2, a lectin from the mushroom Laccaria bicolor, was proven toxic for the model
nematode Caenorhabditis elegans, by binding to nematode specific O‐methylated mannose and fucose
residues in the intestine.
Glycan methylation is widely recognized for bacteria, but is also found in nematodes, snails as wells as
algae and plants, however has not been found on mammalian glycans so far. The biosynthetic pathway
of this specific sugar modification remains still unclear. For Arabidopsis it was shown that methylation
of glucuronic acid takes place in the Golgi, where the methyl group is transferred from the donor
substrate S‐adenosylmethionine to the hydroxyl group of the mature glycan. This donor substrate is
synthesized in the cytosol and has to be transported into the Golgi lumen.
During a forward genetic screen, a C. elegans mutant was identified that is resistant to Tectonin
mediated toxicity and does no longer carry methylated glycans. The mutated gene encodes a protein
of the major facilitator superfamiliy. We hypothesize that this gene product is a Golgi‐localized
transporter, providing the donor substrate required for glycan methylation.
The aim of this project is on the one hand to verify the transport function of this putative transporter
in an in vitro assay and on the other hand, to identify the methyltransferases responsible for producing
these target epitopes. Therefore, I'm expressing candidate genes in insect cells in order to test for
enzyme activity in an in vitro assay.
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
57
Poster session I (Bärlocher – Mannweiler)
1) Kevin Bärlocher
Role of retrograde transport and RidL for intracellular replication of Legionella
2) Katja Becker
Structural and functional analysis of lipoprotein glycosylation in fast‐ and slowgrowing
mycobacteria
3) Desiree Böck
In vivo imaging of Salmonella invasion by electron cryotomography
4) Nathalie Cornillie Expression and characterization of the Plasmodium falciparum & Entamoeba histolytica
Oligosaccharyltransferase
5) Hanna Ebner The evolution of N332 glycan site directed broadly neutralizing antibodies in HIV infection
6) Hyuliya Emurla Asymmetric cell division and barrier function in T cell fate determination
7) Jillianne Eyring Purification and characterization of the octameric oligosaccharyltransferase from
Saccharomyces cerevisiae
8) Susanna Fleurkens Glycoengineering in insect cells to produce carbohydrate‐based vaccines against
Haemonchus contortus
9) Begonia Fudrini Characterization of Mycobacterium smegmatis PafBC
10) Fanny Georgi Correlative Multi‐Modal Imaging for 3D Spheroid Analyses
11) Christoph Gericke The influence of Alzheimer’s Disease‐like amyloid pathology on the immune surveillance in
the brain
12) Lisa Gottschlich Signaling in the General Stress Response of Sphingomonas melonis Fr1
13) Johannes Hartl Dynamic 13C labeling reveals in vivo half‐life of organic coenzymes in exponentially growing
14) Rebecca Higgins Hunt for somatic mutations in Linear Localized Scleroderma
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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15) Mario Hupfeld From protein function to supermolecular structure: Listeria phage A511 baseplate structure
and identification of receptor binding proteins
16) Stephan Isringhausen Dynamics of the bone‐marrow microenvironment during viral infections
17) Ivan Branislav Conformational protection of antibody epitopes on native HIV‐1 envelope glycoprotein
trimmers
18) Martina Lardi Response to nitrogen limitation in Burkholderia phymatum and competition between β‐
rhizobia for legumes infection
19) Katharina Littringer Infection‐induced changes in regulatory T cells
20) Olga Mannweiler Investigation of factors influencing pC3 stability within the Burkholderia cepacia complex
Poster session II (Martini – Zach)
21) Francesca Martini Glyco‐conjugate vaccine against Dirofilaria immitis
22) Corina Mathew N‐linked glycosylation in the Endoplasmatic Reticulum and Golgi
23) Andrea Mauracher Identification of a Novel Genetic Cause of Hypereosinophilia
24) Herbert A. Mbunkah Molecular Epidemiology of Transmitted HIV‐1 Drug Resistance in Drug‐Naive and Newly Diagnosed Patients in Cameroon
25) Fabian Meyer
Methylotrophy ‐ From understanding to engineering
26) Maximilian C.A. Mittelviefhaus Fluidic Force Microscopy ‐ A Novel Technology for Single‐Cell Manipulation and
Micropatterning
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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27) Christina Müller An In vivo study of HIV virus distribution and HIV‐Env specific antibodies in order to eliminate latently infected cells
28) Alessio Mylonas Anti‐TNF promotes type I interferon‐driven psoriasis‐like skin inflammation
29) Nikolas Rakebrandt Infection‐Induced Alterations of CD4+ T Cell Responses upon Heterologous Challenge
30) Felix Rost Impact of Nlrp3 x gut microbiota interactions on experimental colitis and insulin sensitivity
31) Alina Rudnicka
The role of HDAC6/Ubiquitin/aggresome pathway in the influenza virus infection
32) Julia Rühl Combining antigen formulations for human vaccination against cancer
33) Katharina Schmidt MCMV‐Specific T Cell Immunity in the Salivary Gland
34) Carla Sellés‐Moreno
Sickness behavior syndrome and clock gene disregulation in inflammatory bowel disease
35) Leoni Swart
Characterization of Legionella effector proteins involved in the modulation of small
GTPases
36) Aster Vanhecke
Caulobacter crescentus cell division is rate‐limited by peptidoglycan remodeling
37) Oliver Wirz Role of B cells in human rhinovirus infection
38) Kok Yik Lim HIV‐1 Integration Site Patterns in Monocyte‐derived Macrophages and CD4+ T Cells are
“Same Same but Different”
39) Christina Zach Dissecting the biosynthetic pathway of O‐methylated glycans in Caenorhabditis elegans
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
60
Participant details
Name Institute Email
Weronika Barcik SIAF [email protected]
Kevin Bärlocher Institute of Medical Microbiology [email protected]
Isabel Barnstorf Institute of Microbiology [email protected]
Katja Becker Medical Microbiology [email protected]
Desiree Böck Institute for Molecular Biology and Biophysics [email protected]
Nathalie Cornillie Institute of Microbiology [email protected]
Michel Crameri Institute of Medical Virology [email protected]
Hanna Ebner Institute of Medical Virology [email protected]
Hyuliya Emurla Institute of Microbiology and Immunology [email protected]
Jillianne Eyring Institute of Microbiology [email protected]
Susanna Fleurkens Institute of Microbiology [email protected]
Begonia Fudrini Institute of Medical Microbiology [email protected]
Fanny Georgi Institute of Molecular Life Sciences [email protected]
Christoph Gericke Division of Psychiatry Research [email protected]
Lisa Gottschlich Institute of Microbiology lisa‐[email protected]
Johannes Hartl Institute of Microbiology [email protected]
Rebecca Higgins University Hospital [email protected]
Mario Hupfeld INFH [email protected]
Stephan Isringhausen Experimental Hematology [email protected]
Ivan Branislav Institute of Medical Virology [email protected]
Corinna Landig Institute of Microbiology [email protected]
Martina Lardi Plant Biology [email protected]
Dagmara Lewandowska Institute of Medical Virology [email protected]
Katharina Littringer Institute of Experimental Immunology [email protected]
Monica Loi Institute of Experimental Immunology [email protected]
Olga Mannweiler Institute of Plant Biology [email protected]
Sponsored by SUK‐Programm "Doktoratsprogramme" (ETH Zurich & UZH)
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Name Institute Email
Francesca Martini Institute of Microbiology [email protected]
Corina Mathew Institute of Microbiology [email protected]
Andrea Mauracher Paediatric Immunology Children's Hospital Zürich [email protected]
Herbert Afegenwi Mbunkah Division of Infectious Diseases and Hospital Epidemiology
Fabian Meyer Institute of Microbiology [email protected]
Max Mittelviefhaus Institute of Microbiology [email protected]
Christina Müller Division of Infectious Diseases and Hospital Epidemiology
Alessio Mylonas CHUV Dermatology [email protected]
Nikolas Rakebrandt Experimental Immunology [email protected]
Felix Rost Gastroenterology and Hepatology Unit [email protected]
Alina Rudnicka Institute of Molecular Life Sciences [email protected]
Julia Rühl Experimental Immunology [email protected]
Katharina Schmidt Institute of Microbiology [email protected]
Franziska Schönherr Virology [email protected]
Carla Sellés Moreno Institute of Experimental Immunology [email protected]
Bernhard Steiner IMM [email protected]
Emanuel Stiegeler IMV [email protected]
Leoni Swart Medical microbiology [email protected]
Aster Vanhecke EPFL [email protected]
Oliver Wirz SIAF [email protected]
Kok Yik Lim Division of Infectious Diseases & Hospital Edidemiology
Christina Zach Institute of Microbiology [email protected]