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Identification and characterization of novel peroxisomal disorders
Falkenberg, K.D.
Link to publication
Citation for published version (APA):Falkenberg, K. D. (2018). Identification and characterization of novel peroxisomal disorders.
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Download date: 04 Jan 2020
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Chapter 7
Appendix
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Authors’ Contributions Chapter 2: ACBD5 Deficiency Causes a Defect in Peroxisomal Very
Long-Chain Fatty Acid Metabolism
KDF, JK, PM, RJ and CWTR performed laboratory analyses. AP and AV were
responsible for the clinical care of the patient, provided the patient’s clinical
information and revised the manuscript. SF supervised the study and wrote the
manuscript. HRW supervised the study and revised the manuscript. KDF, MS and
RJAW revised the manuscript.
Chapter 3: Allelic Expression Imbalance Promoting a Mutant PEX6
Allele Causes Zellweger Spectrum Disorder
KDF performed genetic and functional studies. KDF and HRW designed genetic
and functional studies. HRW, NEB, SJS, MR, AP and ABM performed Sanger-
sequencing and/or Next Generation Sequencing and independently identified the
PEX6-p.Arg860Trp variant. NEB, ABM, FCCK, AS, ME, KN, FvS, MERG, IKK and
SF contributed clinical and biochemical data and/or fibroblasts of patients. RJAW
and HRW supervised the project. KDF and HRW wrote the manuscript. NEB, ABM,
AS and SF revised the manuscript.
Chapter 4: Heimler Syndrome Is Caused by Hypomorphic Mutations
in the Peroxisome-Biogenesis Genes PEX1 and PEX6
IR, NA-S, SG, GV, JEU, KEC, SGW, NAR, MEA, GCB, HR, AH, AF, SL, NC, KRO,
CELS, CFI, AJM, CE, JAP, MT, SJD, AS, and AAM provided clinical data and patient
material and/or performed Whole Exome Sequencing analyses. KDF performed
functional assays. SF supervised laboratory diagnostic analyses. KDF, MS, WGN,
HRW and GVC wrote and revised the manuscript. WGN, HRW and GVC supervised
the project.
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Chapter 5: Autophagy Inhibitors Do Not Restore Peroxisomal
Functions in Peroxisome Biogenesis Disorders
FCCK and KDF designed and performed experiments, and wrote the manuscript.
RO designed experiments and revised the manuscript. JK performed experiments.
SF supervised laboratory analyses. RJA supervised the study. HRW supervised the
study, designed experiments and revised the manuscript.
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Authors’ AffiliAtions
University of Amsterdam, Amsterdam, the Netherlands
Laboratory Genetic Metabolic Diseases, Academic Medical Center
KD FalkenbergRJA Wanders, PhDHR Waterham, PhDFCC Klouwer, MDR OfmanS Ferdinandusse, PhDJ KosterPA MooyerCWT van Roermund, PhD
Kennedy Krieger Institute, Baltimore, Maryland, USA
R Jones, PhDAB Moser
McGill University, Montreal, Quebec, Canada
Department of Pediatrics and Human Genetics,
NE Braverman, MD
Children’s National Health System, Washington DC, USA
Department of Neurology
A PizzinoA Vanderver, MD
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University of Exeter, Exeter, Devon, UK
College of Life and Environmental Sciences, Biosciences
M Schrader, PhD
Johns Hopkins University School of Medicine, Baltimore, MD, USA
Institute of Genetic Medicine and Department of Neurology,
SJ Steinberg, PhD
Bellvitge Institute for Biomedical Research (IDIBELL), Barcelona, Spain
Neurometabolic Diseases Laboratory, Institute of Neuropathology
A Schlüter, PhDM Ruiz, PhDA Pujol, MD, PhD
Karolinska University Hospital, Stockholm, Sweden
Centre for Inherited Metabolic Diseases
M Engvall, MD, PhDK Naess, MD, PhD
University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Groningen, The Netherlands
Department of Pediatrics
F van Spronsen, MD, PhD
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Maastricht University Medical Center, Maastricht, The Netherlands
Department of Pediatrics
I Körver-Keularts, PhDME Rubio-Gozalbo, MD, PhD
Université Mohammed V, Rabat, Morocco
Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie,
I Ratbi, MDS Guaoua, PhDA Sefiani, MD
Département de Pédodontie-Prévention, Faculté de Médecine Dentaire,
M El Alloussi, MDH Ramdi
University of Antwerp, Antwerp, Belgium
Department of Medical Genetics
M SommenG van Camp, PhDG Vandeweyer, PhD
St. Mary’s Hospital, Manchester Academic Health Sciences Centre, Manchester, UK
Manchester Centre for Genomic Medicine
WG Newman, PhDN Al-SheqaihJE Urquhart, MDKE Chandler, MDSG Williams, MDNA Roberts, PhDGC Black
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University of Manchester, Manchester, UK
Faculty of Life Sciences
AA Mironov, MD, PhD
Schneider Children’s Hospital of Long Island Jewish Medical Center, New Hyde Park, NY, USA
Division of Human Genetics
A Heimler
Liverpool Women’s NHS Foundation Trust, Liverpool, UK
Department of Clinical Genetics
A Fryer, MD
Our Lady’s Children’s Hospital, Crumlin, Dublin, Ireland
National Centre for Medical Genetics
S-A Lynch, MD
Birmingham Women’s Hospital NHS Trust, Birmingham, UK
West Midlands Regional Genetics Service
N Cooper, MDKR Ong, MD
St. James’s University Hospital, University of Leeds, Leeds, UK
Leeds Institute of Biomedical and Clinical Sciences
CEL Smith, PhDCF Inglehearn, AJ Mighell, PhDJA Poulter, PhD
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School of Clinical Dentistry, University of Sheffield, UK
Academic Unit of Oral Health and Development,
C Elcock, PhD
University of Cambridge, Cambridge, UK
Department of Medical Genetics and National Institute for Health Research Cambridge Biomedical Research Centre
M Tischkowitz, PhD
University Hospital of Wales, Cardiff, UK
Institute of Medical Genetics
SJ Davies
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AbbreviAtions
3-MA 3-methyladenine
AAA+ ATPases ATPases Associated with diverse cellular Activities
ABCD1 ATP-binding cassette sub-family D 1 (alternatively known as ALDP)
ABCD2 ATP-binding cassette sub-family D 2 (alternatively known as ALDRP)
ABCD3 ATP-binding cassette sub-family D 3 (alternatively known as PMP70)
ACAA1 3-ketoacyl-CoA thiolase
ACBD5 Acyl-CoA binding domain containing protein 5
ACBP Acyl-CoA binding protein
ACOX1 Acyl-CoA oxidase 1
ACOX2 Branched chain acyl-CoA oxidase
ActD Actinomycin D
AEI Allelic expression imbalance
AGPS Alkyl-glycerone-phosphate synthase (formerly known as alkyl-dihydroxyacetone phosphate synthase or ADHAPS)
AMACR α-methylacyl-CoA racemase
ATP Adenosin-Triphosphate
BAAT Bile acid-CoA:amino acid N- acyltransferase
bp Basepairs
C26:0 Cerotic acid
CA Cholic acid
CDCA Chenodeoxycholic acid
cDNA Copy- or complement-DNA
CNS Central nervous system
CoA Coenzyme A
CPT1 Carnitine palmitoyl-CoA transferase
CQ Chloroquine
CRISPR Clustered Regularly Interspaced Short Palindromic Repeats
DNA Desoxy-ribonucleic acid
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D2 domain ATPase domain (in AAA ATPases)
D3 Deuterated
DBP D-bifunctional protein (alternatively known as multifunctional protein 2, MFP2)
DHAP Dihydroxyacetone phosphate
DHCA Dihydroxycholestanoic acid
DMA Dimethyl acetal
DMEM Dulbecco’s modified Eagle medium
EM Electron microscopy
ER Endoplasmic reticulum
ESI Electrospray ionization
ExAc Exome Aggregation Consortium
FAR1 Fatty acyl-CoA reductase 1
FDA Food and Drug Administration
fw Forward
GATK Genome Analysis Toolkit
gDNA Genomic DNA
GFP Green fluorescent protein
Gly Glycerol
GNPAT Glycerone-phosphate O-acyltransferase (formerly known as dihydroxyacetone phosphate acyltransferase or DHAPAT)
HACL1 2-hydroxyacyl-CoA lyase
HCQ Hydroxychloroquine
HS Heimler syndrome
HUGO Human Genome Organisation
Indel Insertions/deletions
kb Kilobases
kDa Kilo Dalton
L-arg L-arginine
LBP L-bifunctional protein (alternatively known as multifunctional protein 1, MFP1)
LC Liquid chromatography
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lncRNA Long non-coding RNA
MAF Minor allele frequency
miR, miRNA MicroRNA
mRNA Messenger RNA (ribonucleic acid)
MS Mass spectrometry
MRI Magnetic resonance imaging
MRM Multiple reaction monitoring
NAD Nicotinamide adenine dinucleotide
NGS Next Generation Sequencing
PAM Protospacer adjacent motif
PAS Polyadenylation site
PBDs Peroxisome biogenesis disorders
PBD-ZSDs Peroxisome biogenesis disorders within the Zellweger spectrum
PC Phosphatidylcholine,
PEX5L Long isoform of PEX5
PHYH Phytanoyl-CoA hydoxylase
PIPOX L-pipecolate oxidase
PMP Peroxisomal membrane protein
POLII RNA Polymerase II-transcription machinery
PrDH Pristanal dehydrogenase
PTS Peroxisomal targeting signal
PXMP2 Peroxisomal membrane protein 2
RACE Rapid amplification of cDNA ends
RCDP Rhizomelic Chondrodysplasia Punctata
RD Refsum Disease
RT Realtime
rev Reverse
SCPx Sterol carrier protein-X thiolase
SD Standard deviation
SDS Sodium dodecyl sulfate
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SEDs Single Enzyme Deficiencies
SEM Standard error of mean
SKL Peroxisomal targeting signal serine-lysine-leucine (alternatively known as PTS1)
SNHL Sensorineural hearing loss
SNP Single nucleotide polymorphism
SNV Single nucleotide variant
SRH Second region of homology (in ATPases)
ssODN Single-stranded oligo oligodeoxynucleotides
STR Short tandem repeats
TF Transcription factor
THCA Trihydroxycholestanoic acid
UPLC Ultra performance liquid chromatography
UTR Untranslated region
VAPA / VAPB Vesicle-associated membrane protein-associated protein A / B
VLCFAs Very long-chain fatty acids
WES Whole Exome Sequencing
X-ALD X-linked adrenoleukodystrophy
yo Years old
ZSDs Zellweger spectrum disorders
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CurriCulum vitAe
Kim Desiree Falkenberg was born in 1988 in Bocholt, Germany. She finished
secondary school at the St.-Josef Gymnasium in Bocholt, Germany, with an ‘Abitur’
degree in 2007 and started her Bachelor studies in ‘Biosciences’ at the University
of Münster in the same year. After graduating in 2010 she continued her studies
in ‘Biosciences’ at the University of Münster in a M.Sc. course. During this master
course, she spent one semester abroad at the Norwegian University of Science and
Technology (NTNU) in Trondheim, Norway. In 2013, she received her master’s
degree and began her Ph.D. training as an Early Stage Researcher in the Marie
Curie Initial Training Network PerFuMe (Peroxisome Function and Metabolism)
at the Laboratory Genetic Metabolic Diseases at the Academic Medical Center in
Amsterdam, the Netherlands, under supervision of her promotors Hans R. Waterham
and Ronald J.A. Wanders. For four years, she investigated the molecular mechanisms
of peroxisomal diseases, the results of which are presented in this thesis.
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PortfolioYear Work-
load (ECTS)
Courses & workshops
Scientific and laboratory skillsPractical Biostatistics 2013 1.1
Bioinformatics Sequence Analysis 2014 1.1
PerFuMe Workshop I “Systems Biology of metabolic pathways”, Wageningen, NL
2014 1.0
PerFuMe Workshop II “Peroxisomes in Health and Disease”, Exeter, UK
2014 1.0
Bioinformatics 2015 1.1
DNA Technology 2015 2.1
Basic Microscopy 2015 1.6
Advanced qPCR 2016 0.7
Transferable skillsAMC World of Science 2013 0.7
Language Course Dutch (beginners level) 2013
Language Course Dutch (intermediate level) 2014
Oral Presentation in English 2014 0.8
Project Management 2015 0.6
Scientific Writing 2015 1.5
PerFuMe Workshop III “Science in Industry”, Potsdam, DE 2015 1.0
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Presentations
PerFuMe Kick-off conference, Groningen, NLPoster presentation & elevator pitch
2013 0.5
Annual ACM/MDL Meeting, Lunteren, NLPoster presentation
2014 0.5
Marie Sklodowska-Curie Conference (ESOF), Copenhagen, DKPoster presentation
2014 0.5
4th Open European Peroxisome Meeting (OEPM), Neuss, DEOral Presentation
2014 0.5
Annual ACM/MDL Meeting, Lunteren, NLOral Presentation
2015 0.5
Annual ACM/MDL Meeting, Lunteren, NLOral Presentation
2015 0.5
2nd International conference “Peroxisome Formation, Function and Metabolism”, Hamburg, DE
Oral presentation
2016 0.5
5th Open European Peroxisome Meeting (OEPM), Vienna, ATOral presentation
2016 0.5
Attended conferences
PerFuMe Kick-off conference, Groningen, NL 2013 1.0
Marie Skłodowska-Curie Conference: ESOF, Copenhagen, DK 2014 0.5
ACM/MDL Meeting 2014, Lunteren, NL 2014 1.0
4th Open European Peroxisome Meeting (OEPM), Neuss, DE 2014 0.75
ACM/MDL Meeting 2015, Lunteren, NL 2015 1.0
AG&M Meeting 2016, Garderen, NL 2016 1.0
2nd International conference “Peroxisome Formation, Function and Metabolism”, Hamburg, DE
2016 1.0
5th Open European Peroxisome Meeting (OEPM), Vienna, AT 2016 0.75
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Other PhD training
Progress meetings PerFuMe 2013-2016
1.0
Research meetings at Laboratory Genetic Metabolic Diseases, Academic Medical Center Amsterdam, NL
Oral presentations
2013-2017
2.0
Journal club at Laboratory Genetic Metabolic Diseases, Academic Medical Center Amsterdam, NL
Oral presentations
2013-2017
2.0
Secondment I, Exeter, UK 2015 2.5
Secondment II, Sevilla, ES 2015 2.5
Parameters of Esteem
Best Abstract Award, 2nd prizeAG&M Meeting, Garderen, NL
2016
Best Speaker Award, 1st prize2nd International conference “Peroxisome Formation, Function
and Metabolism”, Hamburg, DE
2016
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PubliCAtions * equal contribution
Ratbi I*, Falkenberg KD*, Sommen M* et al.
“Heimler Syndrome Is Caused by Hypomorphic Mutations in the Peroxisome-Biogenesis Genes PEX1 and PEX6.”
Am. J. Hum. Genet. 97, 535-545 (2015). doi:10.1016/j.ajhg.2015.08.011.
Ferdinandusse S*, Falkenberg KD* et al.
“ACBD5 deficiency causes a defect in peroxisomal very long-chain fatty acid metabolism.”
J. Med. Genet. 54(5):330-337 (2017). doi:10.1136/jmedgenet-2016-104132.
Bjørgo K, Fjær R, Mørk HH, Ferdinandusse S, Falkenberg KD et al.
‘Biochemical and genetic characterization of an unusual mild PEX3-related Zellweger spectrum disorder.’
Mol Genet Metab. 121(4):325-328 (2017). doi:10.1016/j.ymgme.2017.06.004.
Falkenberg KD et al.“Allelic Expression Imbalance Promoting a Mutant PEX6 Allele Causes
Zellweger Spectrum Disorder.”Am J Hum Genet. 101(6):965-976 (2017). doi: 10.1016/j.ajhg.2017.11.007.
Falkenberg KD*, Klouwer FCC* et al.
“Autophagy inhibitors do not restore peroxisomal functions in peroxisome biogenesis disorders.”
[manuscript submitted for publication]
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“It takes a VIllage...” – ACknowledgements
This thesis would have never come to its completion without the help of quite a
number of people.
First of all, I’d like to thank my supervisors for their unswerving support. Dear Hans,
thank you for providing me the opportunity to write my PhD thesis in your group.
I could always ask you for advice when struggling, and you helped me re-focus and
re-organize priorities, giving me a shove in the right direction. But most importantly,
you gave me both the chance and the confidence to work rather independently.
Also your stubbornness regarding reviewers’ comments was impressive (and fairly
fruitful), setting a perfect example not to give up too soon. Dear Ronald, your
scientific enthusiasm combined with your encyclopedic knowledge about (probably)
every single metabolic paper ever written was hugely inspirational for me. Thanks for
all your kind words, your open-mindedness and your never-ceasing curiosity.
I consider myself lucky that I could perform my studies in the Laboratory Genetic
Metabolic Diseases, all of its members making it a truly comfortable working
environment. Thanks to each and every one of you for your hospitality and all the
social get-togethers, like lab days, various poules (although I honestly still don’t
entirely get your enthusiasm for the Tour de France) as well as countless gezellige
borrels.
For scientific support, I’d especially like to thank the whole research branch of the
GMZ. Foremost, my gratitude goes to Janet K, who met my countless (and possibly
slightly repetitive) questions with everlasting kindness and the literal patience of a
saint. From day one, I could always count on you, you always made time for me when
I asked for help. Thanks so much! Also without you, Rob O, my thesis would have
definitely lacked quality (and our room wall memorable quotes). Thanks for your
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wonderfully refreshing pragmatic approach to experiments, your huge support was
really a blessing for our whole group.
Dear Carlo, I was inspired by your enthusiasm and your scientific curiosity showing
the heart of a true researcher. I always enjoyed working with you and exchanging
ideas. Dear Lodewijk, thanks for unlimited supply of good advices and especially for
your surprisingly dry humor. You keep the lab (and pipette calibrations) together!
Huge thanks also to Sacha, Petra, Monique, Marjolein and of course the DNA
diagnostic girls, who were always willing to lend experimental help and advice to
me. It was a real pleasure working with you.
I was privileged to not only profit from the resources in the lab GMZ, but to be
also part of the Marie Curie ITN PerFuMe. This brought me in contact with young
researchers with all kind of scientific backgrounds in all over Europe, with the
common goal to decipher the secrets of the best of all organelles. Besides scientific
exchanges, we travelled towns and countries and (by shared experience of progress
meetings, conferences and bachelor parties) we truly developed into so much more
than a just network randomly patched together. I’m so glad I met all of you.
For their hospitality and for everything I learnt during my secondments I’d like to
thank Damien Devos and Nicola, as well Michael Schrader’s lab. Special thanks
to you, Michael, not only for being my official second PerFuMe supervisor but also
for your vast knowledge of immunofluorescence. Thanks (and hugs and kisses) to
Afsoon, for mentoring me during my secondment and for being such a lovable and
cheerful person.
Dear Kathi, you were not only also part of my PerFuMe family, but also my room-
buddy in the office and during conferences. We had a terrific time! Thanks so much
for forgiving me my obvious German-ness, for all the coffee you brought me in just-
too-early meetings, for the experience of sugar-free cake and for being constantly and
reliably there for me throughout the last four years of ups and downs.
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You were also part of our formidable AiO group, to which I want to direct my focus
now. It is said, that a sorrow shared is a sorrow halved, while sharing joy only doubles
it; and in my modest opinion, this was so true for us when sharing the frustrations
and successes of all our projects. I felt that that sharing our research experiences (as
well as piles of cookies) truly bound us together. I knew I could always come to you
to discuss stupid new hypotheses or dinner recipes. And, of course, I will not forget
all our awesome activities, from cake competitions, arts and craft sessions, sunny
lunches, Friday borrels, AiO dinners and Sinterkerst parties up to our trips to the
Lisbon, France and the Efteling (twice!!). Guys, it was truly amazing, you helped me
so much throughout the whole PhD time. Thanks for being there and being you!
Dear Femke, despite your subliminal (word of the day!) OCD, it was a pleasure
working with you and being your next-desk-neighbour. We pretty much hit it
off together, potentially due to sharing a similar kind of (black-ish, occasionally
borderline-offensive) humor. Even on days when I dreaded the thought of going to
the lab, at least I was always looking forward to have a coffee/tea and chat with you.
You made frustrations so much more bearable, and you have this astonishing talent
of cheering me up (mainly by insulting Marte or me). I am so grateful, that we met.
Before risking to get kitschy (and we all know, how much you like that), let me just
say: Thank you so much for everything, honey (particularly also for the legendary
treasure hunt and for agreeing to be my paranymph)!
Dear Marte, although you – as so many in the lab before you – made the unfortunate
choice to turn to the dark side of organelles, I am grateful your companionship in
the last years. How else could I have spread the beauty of German sayings in the
Netherlands? Thanks for your disarming honesty and for being my borrel buddy, my
lovable little soul-ful nerd.
Dear Jia, thanks for your endearing humor and your contagious, almost child-like
excitement and passion for research. Make sure to never lose that. And kudos to you,
girl, you can certainly hold your liquor.
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Dear Clair, thanks for your super-dry humor and your efforts teaching me Dutch
(in merely refusing to talk English with me). Although you were “hesitant” to join us,
you were a welcome princess-like presence in our room, Amsterdams to your very
bones.
Dear Eileen, thanks for your positive spirit, it was always so nice and motivating
talking to you. I admire your aspirations to communicate science to the world and
am really curious where you end up. Research needs people like you!
[To all of these office roomies: Thanks for bearing with my untidiness, slight
unpunctuality, ever-present lab journal complaints and seasonal loops of Christmas
songs. Also thanks to all former office mates, like Kevin, Maxim, Steph, Riekelt and
Naomi, for the great atmosphere and for making it such a fun office to work in.]
Dear Iedan, thanks for your unshaken optimism, all the book recommendations
and your keen interest in science. Despite being the lone bastion of neuroblastoma
research (and the only guy) among the AiOs, you always had an open ear for
everyone’s project, offering valuable input and finding connections to other subjects.
Your organizational skills regarding fairytale themed parks will not be forgotten.
Dear Arwen, your incapability to stop squeaking, when confronted with something
remotely cute, and your crazy science ideas (letting you voluntarily spend weekends
in the lab to test them) make you a true unique in the lab (and probably the world).
Thanks for being so big-hearted and for your awesome moon pies and dumplings.
Dear Jeannette, you granted me asylum when I was homeless. I owe you big thanks
for that, but also for many fun evenings (e.g. the legendary party night with Ntsiki in
Lisbon), for supplying us with fresh fruits and especially for being such a sunny soul.
Dear Ntsiki, you were my coffee buddy, and I will be eternally grateful for the many
times you saved me from coffee-less mornings. With the help of gorgeous flying
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unicorn memes, you always fought yourself out of the worst lab frustrations, and still
had time to listen to my newest “hypothesis”. Thanks for making us have our fantastic
ski trip in France, and for doing your best to motivate us for yoga camps, sunny
lunches and summer schedules.
Dear Suzan, although you seem so quiet and innocent on first sight, we all know by
now about your dark-ish kind of humor accompanied by your adorable dirty laugh. I
admire the stamina you proved when faced with the sorrows of lab work. Thanks for
always having a smile for everyone!
My dear Iliana, of course, I did not forget you. Together we fought through late
evenings in the lab and failed experiments, just like through crowds at all the bars,
concerts, festivals and parades we visited together. I am so grateful for all the time
we spent together (despite the fact that you might be the slowest eater and drinker in
history of humankind). Thanks for being such a laid-back and charming person, and
especially for being always a tiny bit more delayed than I am.
Despite working only with you for a shorter while, I’d like to thank Kevin for all
his help, jokes and peroxisomal enthusiasm, Marco Moedas for the Lisbon trip and
valuable life lessons (i.e. always carry cash), Olga M for sophisticated book talks and
the most beautiful articulation, and Sanne for her quirky sense of humor.
Moreover, I’d like to thank Marco for all the hugs offered when needed and for giggling
through the lab with Marte like two 4 year-old besties. Thanks to you, Rashmi, for
your warm and calm presence, and always having a nice word for everyone. Also
thanks to former members of the lab, Anita, Sandra, Olga P, Eveline, Eugen and
Martin, for your help and all your good advises.
I especially also like to thank you, Riekelt, for your constant interest in my projects,
your help with my application, and for your willingness to improve your German
pronunciation. To you and Naomi, Reuben, Alyson, Rob W, Michel and Fred I also
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owe many enlightening conversations during borrels. Special thanks to Michel for
clearing out my desk and taking care of the kids.
Apart from all those people helping with my research, I would also like to express my
gratitude to the people who kept me sane(-ish) during the last years.
Meine lieben Couch Potatoes, da ich den Eindruck hatte, dass ihr mein Projekt leicht
missverstanden habt (nämlich der festen Meinung seid, dass ich an gefährlichen
Viren arbeite mit dem erklärten Ziel, die Weltherrschaft zu ergreifen), hoffe ich
nun, dass euch diese Doktorarbeit vom Gegenteil überzeugt. Lieben Dank euch
für Bootstouren, Strandtrips und zahllose Dinner- und Bar-Abende. Toll, dass ich
zusammen mit euch Amsterdam entdecken durfte. Mit dem Niederländisch hat es
dann ja auch fast geklappt. Danke für alles!
Auch dicken Dank an Laura, Anna und Anne, dafür dass ihr mich so perfekt vom
Alltag abgelenkt hat. Mit euch ist es immer noch genauso lustig und ungezwungen,
als hätten wir gestern noch die Schulbank gedrückt. Die Reisen nach Rom, Kanada
und Australien waren einfach toll!
Zu guter Letzt möchte ich meiner Familie danken. Ich fürchte ein wenig, dass diese
Zeilen schwerlich daran herangekommen, wie dankbar ich euch allen tatsächlich
bin, aber ich werde mein Bestes tun. Ihr seid immer und unerschütterlich für mich
da, und zeigt sogar Interesse für meine Projekte, auch wenn es noch so nerdig wird.
Danke Oma, dass du mich immer mit offenen Armen empfängst (und natürlich
für die Riesenladung Spritzgebäck jeden Winter). Danke Linda (meiner Einhorn-
Paranymphe) und Christian, dass ihr in meinem Leben seid, dass ihr mich zum
Lachen bringt, für die Hilfe beim Cover (auch wenn blau-gelben Punkte letztendlich
doch das Nachsehen hatten), und vor allem für Oscar, mit dem die Welt doch noch
tausend mal so bunt und sonnig scheint.
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Besonderer Dank geht natürlich an meine Eltern. Liebe Mama, lieber Papa, danke für
eure ehrlichen Kritiken und Ratschläge, für eure uneingeschränkte Unterstützung in
allen Lebenslagen (und bei zahlreichen Umzügen) und für die Gewissheit, dass ich
mich hundertprozentig auf euch verlassen kann (und egal was ihr sagt, das ist bei
Weitem nicht selbstverständlich). Ihr seid für mich wie ein sicherer Hafen, in den ich
immer zurückkehren kann, wie unruhig es sonst auch ist. Ich bin unglaublich stolz
und glücklich, euch alle zu haben. Ich hab euch sehr lieb.
Knowing myself, there is a pretty high chance that some people, which I owe my
gratitude to, slipped my mind (including for instance quite a number of students).
For all those forgotten: Thanks a lot, guys (and my sincere apologies)!!
Out of respect and a healthy portion of self-preservation, I decided to refrain from
adding any photographic memoirs to this section. But be not be mistaken, my friends,
they will all be stored at a safe place.
Till then, I wish you farewell and all the best for your future.
Thanks for having joint the ride, it’s been a blast.
Yours,
Kim