Roadmap for the Bioinformatics and Systems Biology Activities of Dr. Eduardo Mendoza (Version 1.1, April 15, 2010) 1. Introduction to the BSB Roadmap When I moved in late 2002 from the software industry back to academe in order to contribute to Philippine S & T, I had a period of around 10 years in mind to try to achieve the research, education and technology transfer impact which I thought would be possible with Bioinformatics and Systems Biology (BSB). The basic idea was to establish computational groups, which would work very closely with experimental (and later clinical) groups, both in the Philippines and abroad, and do leading-edge research. My preliminary visit in May/June 2002 convinced me that a feasible strategy was:

• Phase 1: Establish a Community of Practice (CoP) and educational activities first at UP Diliman (the result was the SMILES initiative)

• Phase 2: Cultivate CoPs in further universities and institutions to broaden the base for BSB (MBaRC, various other projects)

• Phase 3: Explore ways of institutionalizing these activities at various levels and in various institutions

In hindsight, Phase 1 can now appropriately be mapped to the first 5 years (Jan 2003 to year end 2007). I chose to start Phase 2 with my first BalikScientist visit (Feb – Apr 2008). I also devoted a large part of the second visit (Nov/Dec 2008 and June/August 2009) to this effort while already looking at ways of initiating Phase 3. The progress made since January 2003 (when I conducted my first visit towards this goal) has certainly exceeded my initial expectations.

Details are provided in the succeeding sections and in the references.

SMILES and SMILES and MBaRCMBaRC: : PinoyPinoy InititativesInititatives forforBioinformaticsBioinformatics and Systems Biologyand Systems Biology

SMILESSMILES??

• Is a multidisciplinary „bottom-up“R & ER & E initiative at UP Dilimanfocussed on novel computationalapplications in the Life & Environmental Sciences

• began in March 2003 with Joint Experimenter-Modeller (JEMJEM) projects to evolve a CommunityCommunityof of PracticePractice ((CoPCoP))

•• OverOver 25 25 projectsprojects inclincl: EUCLIS, : EUCLIS, theWePtheWeP, DOPA, DOPA--KID, HANAPIN, KID, HANAPIN, GWAPO,GWAPO,……

MBaRCMBaRC: : MManilaanila BaBayy RResearchesearch CCorridororridor

•• An initiative An initiative forfor ComputationalComputational Life Life Sciences Sciences betweenbetween::–– DLSU ManilaDLSU Manila College of Science & College of Science &

College of Computer College of Computer StudiesStudies–– UP ManilaUP Manila College of Arts & Sciences College of Arts & Sciences

& College of & College of MedicineMedicine–– MapuaMapua School of School of GraduateGraduate StudiesStudies & &

DeptDept of Information Technologyof Information Technology•• Projects (Projects (MarchMarch 2008 2008 --): ):

MADManMADMan, , VirhoLexVirhoLex, HANAPIN, , HANAPIN, CaMBioCaMBio, , PhilSHIFTPhilSHIFT,,……

CurrentCurrent scorecardscorecard::•• Research:Research: > 26 international (> 26 international (mostlymost ly ISI) ISI) publicationspublications•• EducationEducation:: 4 PhD, 15 MS 4 PhD, 15 MS graduatesgraduates, 4 , 4 PostdocsPostdocs;;

7 (+ 2) PhD 6 MS7 (+ 2) PhD, 6 MS studentsstudents

2. Overall Research Impact The initiatives SMILES (Statistics, Mathematics and Informatics in the Life and Environmental Sciences) at UP Diliman and MBaRC (Manila Bay Research Corridor) at De la Salle Manila, UP Manila and Mapua, which started in March 2003 and March 2008 respectively, have established an early Filipino “foothold” in the now widely-acknowledged strategic fields of Bioinformatics and Systems Biology (BSB). Evidence for this “foothold is provided by i) currently 28 papers published in international ( ~ 22 ISI) journals by participants of SMILES and MBaRC(s. Section 3),ii) the holding of the 10th International Conference on Molecular Systems Biology at UP Diliman (Feb 2008) and iii) the participation of Filipino researchers and students in significant, internationally-funded research in the field (s. Section 3). For more details on the importance of BSB for the fields of Biomedicine and Biotechnology, please confer the review “Systems Biology: its Past, Present and Potential” published in Philippine Science Letters (Vol 2, No 1, August 2009).

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3. International Journal Publications The SMILES and MBaRC initiatives focussed from the beginning on publishing in international journals in order to benefit from the feedback of international experts (peer-review process) and to promote international recognition of Filipino research in the field. The following is the list of international journal publications from participants of (names are highlighted in bold, current as of March 15, 2010): 1. del Rosario RCH, Oppawsky C, Tittor J, Oesterhelt D. Modeling the membrane potential

generation of bacteriorhodopsin. Mathematical biosciences 2010;225(1):68-80 2. Naval PC, Sison LG, Mendoza ER. Parameter estimation with Term-wise Decomposition in

Biochemical Network GMA Models by Hybrid Regularized Least Squares-Particle Swarm Optimization. Proceedings of the IEEE Conference on Evolutionary Computation (CEC) 2010, July 18-23, 2010, Barcelona, Spain (in press).

3. Gonzalez O, Oberwinkler T, Mansueto, L, Pfeiffer F, Mendoza ER, Zimmer R, Oesterhelt D. Characterization of growth and metabólism of the Haloalkaliphile Natronomonas pharaonis. 2009, PLoS Computational Biology (in press).

4. Dulam-Banawa B, Marin-Sanguino A, Mendoza ER. The evolution of synapse models: from numbers to networks to spaces. Pharmacopyschiatry May 2010 (in press).

5. Hohner A, David MPC, Rädler JO. Controlled solvent-exchange deposition of phospholipid membranes onto solid surfaces. Biointerphases 2010 (in press)

6. Schwake G, Youssef S, Kuhr JT, Gude S, David MPC, Mendoza ER, Frey E, Rädler JO, Predictive modeling of non-viral gene transfer, 2009. Journal of Biotechnology and Bioengineering (in press)

7. Mendoza ER. From communicational to computational: systems modeling approaches for psychiatric research. In “Systems Biology and Psychiatric Research” Tretter F, Gebicke-Härter P, Winterer G, Mendoza ER (Eds) Wiley VCH 2010 (in press).

8. Marin-Sanguino A, Mendoza ER, Voit EO, Flux Duality in Non-Linear GMA Systems: Implications for Metabolic Engineering, Journal of Biotechnology, 2009 (in press)

9. del Rosario RCH, Diener F, Diener M, Oesterhelt D. The steady-state phase distribution of the motor switch complex model of Halobacterium salinarum. Mathematical Biosciences 222, 2009; 117-126.

10. David MPC, Bantang, JY, Mendoza ER, Modeling atonal membrane reactions with the projective brane calculus PABM, Electronic Proceedings in Theoretical Computer Science (Sept 2009)

11. Mendoza ER, Systems Biology: Its Past, Present and Potential. Phil Science Letters, Vol 2, No 1 Aug 2009 (available online at http://www.philsciletters.org/ )

12. David MPC, Bantang, JY, Mendoza ER, A Projective Brane Calculus based on Activate, Bud and Mate Primitives, Transactions on Computational Systems Biology, Special issue on "Computational models for cell processes", Sept 2009 .

13. Rodriguez EM, Rudy A, del Rosario RCH, Vollmar A, Mendoza ER, A DiscretePetri Net Model for Cephalostatin-induced Apoptosis in Leukemic Cells, Natural Computing, Aug 2009

14. del Rosario RCH, Mendoza ER, Oesterhelt D. Modelling the Bioenergetics of Halobacterium salinarum with Petri Nets, Journal of Computational and Theoretical Nanotechnology Aug 2009

15. Marin-Sanguino A, del Rosario RCH , Mendoza ER. Concept Maps and Canonical Models in Neuropsychiatry. Pharmacopsychiatry. 2009;42 Suppl 1:S51-8.

16. Gonzalez O, Gronau S, Pfeiffer F, Mendoza ER, Zimmer R, Oesterhelt D. Systems Analysis of Bioenergetics and Growth of the Extreme Halophile Halobacterium salinarum . 2009, PLoS Computational Biology, Vol 5, Issue 4

17. Marin-Sanguino A, Torres, NV, Mendoza ER, Oesterhelt D, Metabolic Engineering with Power-Law and linear logarithmic Systems, Mathematical Biosciences, 2009; Vol 218, 50-8.

18. del Rosario RCH, Mendoza ER, Voit EO. Challenges in lin-log modelling of glycolysis in Lactococcus lactis. IET Systems Biology. 2008;2:136-30.

19. Marin-Sanguino A, Mendoza ER. Hybrid modeling in computational neuropsychiatry. Pharmacopsychiatry. 2008;41 Suppl 1:S85-8.

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20. Roenneberg T, Chua EJ, Bernardo R, Mendoza ER. Modelling biological rhythms. Curr Biol. 2008;18:R826-35.

21. Bruskewich R et al, including M. Echavez, K. Manansala, J.M. Yap, The Generation Challenge Programme Platform: Semantic Standards and Workbench for Crop Science, International Journal of Plant Genomics, May 2008, Article ID 369601, 6 pages

22. Gonzalez O, Zimmer R, Assigning functional linkages to proteins using phylogenetic profiles and continuous phenotypes, Bioinformatics, May 2008,Vol. 24, No. 10

23. David MPC, Lapid C, Daria V, An efficient visualization tool for the analysis of protein mutant matrices, BMC Bioinformatics, April 2008, 9: 218

24. Falb M, Müller K, Königsmayer L, Oberwinkler T, Horn P, von Gronau S, Gonzalez O, Pfeiffer F, Bornberg-Bauer F, Oesterhelt D. Metabolism of halophilic archea, Extremophiles, February 2008, 12, pp. 177-196

25. Gonzalez O, Gronau S, Falb M, Pfeiffer F, Mendoza ER, Zimmer R, Oesterhelt D. Reconstruction, modeling & analysis of Halobacterium salinarum R-1 metabolism. Mol Biosys. 2008;3:148-59.

26. del Rosario RCH, Staudinger WF, Streif S, Pfeiffer F, Mendoza ER, Oesterhelt D. Modelling the CheY (D10K,Y100W) Halobacterium salinarum mutant: sensitivity analysis allows choice of parameter to be modified in the phototaxis model. IET Systems Biology. 2007;1:207-2.

27. Batista RT, Ramirez DB, Santos RD, del Rosario MC, Mendoza ER. EUCLIS--an information system for circadian systems biology. IET Syst Biol. 2007;1:266-73.

28. Gonzalez OR, Kuper C, Jung K, Naval PC, Mendoza ER. Parameter estimation using simulated annealing for S-system models of biochemical networks. Bioinformatics. 2007;23: 480-6.

29. Dizon R, Yap HT, Understanding coral reefs as complex systems: degradation and prospects for recovery, Scientia Marina 70 (2), June 2006, p. 219-226

The following papers are submitted or to be submitted shortly: 1. Bantang JY, Reichl U, Mendoza ER. An efficient algorithm for generating the time-dependent

probability density function describing low-count well-stirred chemical reactive systems. 2009 (to be submitted to Philippine Science Letters)

2. Talaue, CO, del Rosario RCH, Pfeiffer F, Mendoza ER, Oesterhelt D. Model construction and Analysis of Respiration in Halobacterium salinarum. (to be submitted)

4. Organization of Research Collaborations and Conferences 4.1 Roadmaps of the individual Projects and Research Collaborations For convenience, we begin with the newer projects, particularly those initiated during the BalikScientist stays (2008 – present). 4.1.1 MADMan (Munich-Atlanta-Diliman-Manila), Phase 1 (Mar 2008 – Jun 2009) Project description

This was started in March 2008 as part of the 1st BalikScientist visit, extending the MAD initative (which began Aug 2006 between LMU in Munich, Georgia Tech in Atlanta and UP in Diliman) to the MBaRC

participants from Manila. Goal is to establish a benchmarking platform and process for BST parameter estimation algorithms. It was carried out initially by DLSU Manila and Mapua researchers and students However for lack of resources, Mapua was not able to continue its involvement (1 Faculty member discontinued participation in Jan 2009 due to PhD scholarship abroad, another got sick). 5 MS Computer Science students from DLSU started their MS theses, 2 graduated in 2009. Collaboration partners: Eberhard Voit (Integrated Biosystems Institute, Georgia Tech), Alberto Marin-Sanguino (Max Planck Institute of Biochemistry, Munich), Ricardo del Rosario (Genome Institute of Singapore)

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Impact Assessment: • The MADMan activities are cited in the review paper “Recent Developments in Parameter

Estimation and Structure Identification of Biochemical and Genomic Systems” by I. Chou and E. Voit” in the international journal “Mathematical Biosciences” (January 2009)

• 4 MS theses (2 at DLSU Manila, 2 at UP Diliman were completed in 2008/09, 2 PhD studies (focussed on Systems Biology) are ongoing (details in Educational Impact doc)

Outlook • The other 3 MS students at DLSU are currently working full-time in a software company but have

signified their interest in finishing the course later (which would re-activate the activities initiated) • Since modeling with Biochemical Systems Theory remains an important research area for me and

my students (now also Professors at various universities), further MS theses will be assigned as appropriate to further extend the MADMan work.

4.1.2 CaMBio (Canonical Modeling by Bioscientists and –technolgists) User Interface,

April 09 - present Project description: The CaMBio project was started about 2 years ago at the Max Planck Institute of Biochemistry and is led by Dr. Alberto Marin-Sanguino. The goal is to develop a

software platform that based on open access/source software and easy enough for bioscientists and biotechnologists to use as part of their research work. The methods (and tools supporting them) should easily understandable to allow incremental refinement of

models as more data, information and knowledge are integrated into the process. CaMBio is hence based on stoichiometric (qualitative) and canonical (deterministic ODE) modeling approaches. The platform used is the open access software Scilab (developed by INRIA France). Two senior Computer Science students from UP Manila and their mentor, Richard Bryann Chua are involved in the project since April 2009 – their task is mainly to develop the User Interface for the software platform. The first release is planned for April 2010. Collaboration partners: Eberhard Voit (Integrated Biosystems Institute, Georgia Tech), Alberto Marin-Sanguino, Dieter Oesterhelt (Max Planck Institute of Biochemistry, Munich) Impact Assessment: • A number of user groups in various countries (Germany, Austria, Spain,..) are already

waiting to use the software Outlook: • I am currently looking for groups of bioscientists and biotechnologists in the Philippines

who can pilot the use of CaMBio • The software has a lot of potential users and could be developed further by students in the

Philippines, particularly at UP Manila 4.1.3 VirhoLex (Virus-host interaction Lexicon), Phase 1 (Mar 2008 – Mar 2010) Project description

This is the second project which also started in March 2008 from the 1st BalikScientist stay. The software for VirhoLex was implemented by reusing some of the modules of EUCLIS (with the permission of the EUCLOCK Steering Committee, of which Dr. Mendoza is a member) according to the requirements of various virologists working on influenza A and dengue. The work was done was senior year projects of 6 BS Comp Sci students from UP Manila Department of Physical Sciences and Mathematics

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(DPSM) and 5 BS Computer Science students in DLSU. Mentoring was done by 1 faculty member at DLSU (Mr. Ap-apid) and 4 faculty members at UP Manila (Mr. R. Chua, Mrs. S. Magboo, Dr. P. Magboo and Mr. G. Solano). The use of a professional software framework (MSF) enabled good interaction with the virologists as well a well-managed development process despite the lack of experience of the students. Version 1.0 is ready for release and is being installed at the Max-Planck-Institute High Performance Computing Center (to provide high availability and professional maintenance) to be available for the worldwide community of virologists by April 1, 2010. Collaboration Partners: Udo Reichl (Max Planck Institute, Magdeburg, Germany), Jürgen Haas (University of Edinburgh, UK), Raul Destura (UP Manila), Markus Rampp (Max Planck Society HPC Center) Impact Assessment: • With the release of V1.0, this will be (one of?) the first information system(s) for Systems

Virology – again made in the Philippines! • The information on influenza A and dengue will potentially be used for storing information

regarding the genome library being developed by the group of Dr. Raul Destura at the NIH Institute of

• A paper was presented at the annual NIMBUS meeting (Manila, Nov 09) by S. Magboo Outlook • Paper submission to an international journal planned by the end of the year (based on the first year

of the system’s use /availability to the worldwide research community) • An article on VirhoLex will be written for the “Star Science” series of the Philippine STAR in

March/April 2010 • Successful BS Comp Sci project work for 6 students at UP Manila and 5 students at DLSU

established V1.0 of the System. Further senior student projects can be based on further development of the system

• An important further collaboration with Dr. Destura of NIH will involve new approaches to TB research (s. below). It will probably be necessary to extend VirhoLex to handle information on bacterial pathogens, such the MTBC (Mycobacterium tuberculosis complex) and rename the system as PathoLex (Pathogen host interaction Lexicon).

4.1.4 PhilSHIFT (Philippine Shiftwork and Health -Interdisciplinary concepts, Fieldwork

and Translational research, Nov 2008 – present) Project description This project was initiated in Nov 2008 during the 1st part of the 2nd BalikScientist stay and will impact the health and productivity of shift workers in the fast growing call center and BPO industry in the Philippines. This research builds on the work done in the ClockWork project (funded by the Daimler-Benz Foundation) which seeks to use the newest chronobiological findings (esp. individuality of the biological clock) to provide approaches and tools to manage shift schedules and work environment to maximize productivity and minimize health risks. Projects in Germany were done with Siemens and Mercedes Benz, but primarily in the factory environment. Conducting such a project will not only be beneficial to Filipino call center workers and companies but also provide new research insights. Collaboration Partners: Center for Chronobiology, Institute of Medical Psychology at LMU (headed by Till Roenneberg). A MOA was signed between T. Roenneberg and UP Manila Chancellor R. Arcadio on July 31, 2009.

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Impact Assessment: • Joint UP Manila-LMU Symposium on “Shift Work and Health Research” on Jul 31 with

renowned LMU chronobiologist Prof. Till Roenneberg (around 70 participants) • Hands-on Research Training at shift-work projects at Siemens for UP Manila Co-Investigators Dr.

Darwin Dasig and Mrs. Marilie Ruiz-Aguila in Munich and Berlin (Sept-Oct 2009) • Follow up Research Colloquium (with research methods training for Phil. Researchers interested

in shift work and health research) organized for Feb 6, 2010 (with Ms. Celine Vetter, Project Leader from LMU Institute of Medical Psychology)

• A Community of Practice (named “PhilSHIFT Community”) was established on Feb 6 as a medium of exchange of knowledge; a repository of relevant papers, studies and other material for research on Chronobiology and Shiftwork has been set up at EUCLIS.

Outlook • Proposed schedule for the PhilSHIFT projects

and corresponding proposals to PCHRD in preparation (led by D. Dasig, M. Ruiz-Aguila and with my support)

• Press Conference organized by DOST BSP on March 24 to launch the PhilMCTQ subproject (determining the Filipino chronotype profile, which will serve as reference to detect changes effected by shiftwork)

• Meeting with Call Center managers to be organized by DOST BSP with the ultimate goal of recruiting 1-2 companies for the initial field studies

• UP Manila involvement in a planned proposal “SHIFT” for the EU FP7 HEALTH 2011 Call for Proposals

PhilSHIFTPhilSHIFT Project Plan Project Plan (Status: Feb 25, 2010)(Status: Feb 25, 2010)

F eb '11Jan '11Dec '10Nov '1 0Oct '1 0Sep '10Au g '10Jul '10Jun '1 0Ma y '1 0Apr '1 0M ar '10

PhilMCTQPhilMCTQEstablishEstab lish Fil ipino Fil ipino chronotypechronotype profileprofilewithwith WePWeP 1.01.0

PhilSHIFTPhilSHIFT--CCCCFieldField StudiesStudies in 1in 1-- 2 2

CallCal l CentersCenters

PhilSHIFTPhilSHIFT--HWHW

FieldField StudiesStudies forforHealth Health workersworkers

M 1 M1 –– Mar 8 Mar 8 PhilM CTQPhilMCTQ availableavail able on on WePWeP 1.01.0M 2 M2 –– Mar 12 UPM Mar 12 UPM E thicsE thics approvalapproval obtainedobtainedM 3 M3 –– Mar 12 Mar 12 submissionsubmission of PCHRD of PCHRD ProposalProposal 11M 4M4–– Mar 15 Mar 15 oror 16 Press 16 P ress confconf to to launchlaunch PhilMCTQPhilMCTQ act ivi ties4act ivit ies4M 5M5-- Mar 17 Mar 17 -- ongoingongoing activ iti esactiv ities to to promotepromote Phi lMCT QPhil MCTQ in in variousvariouspartsparts of of thethe count rycount ry

M1 M1 M2, M 3, M 4, M 5 M2, M 3, M 4, M5 ……

C1 C1 –– WeekWeek of Mar 22of Mar 22--25 25 AwarenessAwareness eventevent forfor CallCall Center ManagersCenter ManagersC2 C2 –– MarMar--AprApr: : selectionselect ion and and negotiationnegot iation withwith 11--2 2 callcall centerscentersC3 C3 –– May 2011; May 2011; submissionsubmission of PCHRD of PCHRD ProposalP roposal 22C4C4–– Jun eJune --JulyJuly 2 011 20 11 Pre pPre p pha sepha se of of fieldf ield stu dystud yC5 C5 ––JulyJuly 201 1: 2011 : WePWeP 1.5 (1.5 ( PocketPCPocketPC softwar esoftwar e o n o n callcall cen tercent er a genta gent workstat io nwo rkstatio n ava ila bleava ilab le))C6 C6 –– AugAug--SepSep 2011 2011 FieldField studystudy conductedconductedC7 C7 –– OctOct --DecDec 2011 Analysis and 2011 Analysis and evaluat ionevaluat ion of of f iel dfi eld studystudy datadataC8 C8 ––´́F eb 2011 2nd Research Symposium on Feb 2011 2nd Research Symposium on ChronobiologyChronobiology and and Shif tworkShif twork ((withwith prelprel. . ResultsResults reportreport))C9 C9 –– ongoingongoing cult ivat ioncult ivati on of of PhilSHIFTPhilSHIF T CoPCoP

H1 H1 –– DecDec 2010: 2010: init ialinitial planningplanning forfor Health Industry Health Industry studiesstudiesH2 H2 –– Jan 2011: Submission of PCHRD Jan 2011: Submission of PCHRD ProposalProposal 33A3 A3 –– Feb 2011 Feb 2011 LaunchLaunch of of PhilSHIFTPhilSHIFT--HWHW at at Research ColloquiumResearch Colloquium

C1C1 C2C2 C3C3 C4C4 C5C5 C6C6 C7C7C8C8

H1H1 H2H2 H3H3

4.1.5 HANAPIN-SP (Health Applications of NAtural Products INformation-System for

Plants, Nov 08 - present) Project description The HANAPIN activities were started in Nov 2008 (1st Phase of the 2nd BSP visit) originally focussed only on marine natural products (as part of the main objective of the BSP visit – to support the activities of MSI, in particular with regard to the PharmaSeas project. Independently, an initiative for an information system for Plant Natural Products was initiated by Dr. Maricon Carillo at UP Manila. When Dr. Mendoza heard about this, he made it a point to synchronize the efforts with those at UP Diliman in order to achieve the apparent synergies. This was accomplished and the two teams are now working closely together. They are guided by requirements coming from Natural Products experts at UP Diliman (Dr. G. Concepcion, Dr. I. Villaseñor, Dr. E. Ramos) and at UP Manila (especially for phytochemicals). The work is still ongoing and the first two phases are expected to last at least till end of 2011.

NaturalNatural ProductsProducts OntologyOntology and HANAPIN and HANAPIN SystemsSystems•• A formal A formal ontologyontology ((currentlycurrently lackinglacking in in

NP NP researchresearch) will ) will enableenable moremore openopeninfoinfo infrastructureinfrastructure forfor thethe communitycommunity

•• HANAPIN (Health HANAPIN (Health ApplicationApplication of of NaturalNatural ProductsProducts Information) Information) systemssystemsuseuse NPO as NPO as basisbasis

•• K. Manansala (UPD MSCS K. Manansala (UPD MSCS candcand), J. ), J. Panibe (UPM MS Health Panibe (UPM MS Health InformaticsInformaticsstud.), R. Batistastud.), R. Batista--Navarro (PhD Navarro (PhD studentstudentat Manchester University), M. at Manchester University), M. CarilloCarillo, , M. Endriga, R.B. M. Endriga, R.B. Chua,GChua,G. Solano (all . Solano (all UPM)UPM)

•• Partners:Partners:–– G. Concepcion (UPD MSI)G. Concepcion (UPD MSI)–– I. I . VillaseVillaseññoror, E. Amor (UPD IC), E. Amor (UPD IC)

•• HANAPINHANAPIN--SP (System SP (System forfor Plant NP) Plant NP) and HANAPINand HANAPIN--SM (System SM (System forfor Marine Marine NP) NP) underunder developmentdevelopment byby UPM and UPM and UPD UPD respectivelyrespectively

Collaboration Partners: Giselle Concepcion , Irene Villaseñor, Evangeline Ramos (all UP Diliman) Impact Assessment: At UP Manila: • UP Manila team has submited a proposal to PCHRD regarding support for the development of the

plant NPO-oriented parts

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• Training of Mr. Panibe and 2 other MSHI students through joint course offering “Introduction to Systems Biology” for UP Manila and UP Diliman (ongoing courses this semester till March 19, 2010)

Outlook • MS Thesis by Jerome Panibe will extend the NPO Release 1.0 (mainly on marine NPOs) to plant

NPOs (target completion late 2011) • Collaboration with UPLB Computer Science (Mr. J. Pabico) on

interoperability/compatibility with the information system on plant natural products being developed there (possibly thru use of the Natural Products Ontology)

4.1.6 New activities/projects initiated in the current BalikScientist visit (Feb/Mar 2010) • Collaboration with the NIH Institute of Molecular Biology and Biotechnology over the

next 3 years on the recently approved grant proposals on the Dengue Diagnostic Kit, genome library for influenza A and new approaches for MTBC research: this is the results of 2 meetings and extensive email communication. A definite action item is to set up an international consortium to respond to the Dengue call item in FP7-HEALTH-2011 call (final version July 30, submission deadline is Oct/Nov 2010)

• Extension of the current collaboration with Dr. F. Roa, PGH Dermatology Dept (s. PHOTOPSOR project of UP Diliman, s. below) to encompass the molecular level and more comprehensively understand the influence of dopamine in the epidermal melanin unit processes—this project would be called DOPA-MEL

• Potential participation of various colleges/institutes/departments of UP Manila in upcoming EU Framework Program 7 (FP7) Calls for Proposal on HEALTH, ENVIRONMENT and ICT : meeting is scheduled for March 17 with participants from various departments and institutes

• Collaboration with Dept of Neuroscience and Dept of Psychiatry of UP College of Medicine on bipolar disorder and other mental disorders: an initial meeting took place on Feb 24, 2010, where I presented the work done in neuroscience/-psychiatry so far

• Collaboration with Alvin Marcelo (National TeleHealth Project) on the use of Mobia Modeler (a software platform developed by Florence Balagtas-Fernandez as part of her PhD thesis at LMU)

4.1.7 TOPOGEO (Jan 2009 - )

Project description: TopologyTopology--basedbased geometricgeometric modelingmodeling of of membranemembrane „„pearlingpearling““ ((workwork in in progressprogress))

• Actin deprivation of Dictyostelium cell causesmembrane „pearling“– Experimental collaborators:

Doris Heinrich group (LMU)• PhD thesis work of R. Ap-

apid (DLSU Manila)– Extension of Damiand group

methods & software (LIRIS Lyon, France)

– Mapping of operations on generalized maps to PABM extensions

This is an initial venture into the approach formulated in more general terms in the MiMEMP proposal (s. Section 4.1.16). The method used is based on the “topology-based geometric modeling” developed by G, Damiand’s lab in Lyon, France on the basis of the “topological map” concept, a variant of the classical 3D “combinatorial map” concept . Collaboration Parnter: D. Heinrich (LMU Physics), G. Damiand (Lyon), J. Bantang (NIP, UP Diliman)

Impact Assessment: with this PhD thesis work, we are also exploring the feasibility of one of the approaches proposed in MiMEMP Outlook: • The PhD thesis work of R. Ap-apid is targeted to be finished by Q4 2010 or Q1 2011

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• If the proposal is successful (decision in May/June 2010, the MIMeMP schedule is start work in the same timeframe, so that the results will indeed be good input for further research

4.1.8 ChronoSPA (Oct 2005 – present) Project description: This project studies the feasibility of stochastic process algebra (SPA) to modeling more complex models of circadian systems. A number of authors have published stochastic pi calculus and BioPEPA models of the basic component of circadian models, the Transcription-Translation Loop (TTL), but examples of more complex (and realistic) ones are still missing. A part of the PhD thesis of Elain Jane Chua (on leave from DLSU Manila) at TU München is to apply SPA techniques to the Roenneberg-Merrow model, which belongs to the family of evolutionary circadian clock models. Collaboration Partners: Manfred Broy (TU München Informatics), Till Roenneberg (LMU Medical School) Impact Assessment: if successful, this will be first SPA model of a circadian system beyond the basic TTL Outlook: this can be extended to more complex models such as those for mammalian circadian systems. 4.1.9 EUCLIS (EUCLOCK Information System, http://www.bioinfo.mpg.de/euclis/, Jan

2006 – Dec 2010) Project Description: EUCLIS is Work Package D.1 of the EUCLOCK project (http://www.euclock.org/ ), a 5-year Integrated Project of the 6th EU Framework Program (FP6) funded with 16 million Euros. When invited to lead the work, I stipulated the involvement of graduate Research Assistants from UP

Diliman. From Jan 2006 till Dec 2010, 4-5 RA’s have designed and developed the software. Total funding for EUCLIS is 150 000 Euros. The European Biological Rhythms Society (EBRS) plans to support and maintain the system beyond the duration of the EUCLOCK project. Collaboration Partners: 29 leading Chronobiology research labs in Europe, 3 innovative SMEs and the Max Planck Society High Performance Computing Center in Garching, Germany Impact Assessment:

• The system is now becoming an essential part of the information infrastructure of the worldwide Chronobiology research community, which is a scientific contribution of significant impact.

• Numerous research posters and talks have been presented at international and national conferences, most significantly at the 7th International Conference on Systems Biology (Yokohama, Oct 2006) and at Joint Meeting of the European Biological Rhythms Society and the Japanese Society for Chronobiology (Strasburg, France, Aug 2009). 2 ISI publications resulted from this project so far.

• The project has reated contacts which led to subsequent projects such as the WeP (Worldwide experimental Platform) and PhilSHIFT—more details below.

• It has provided funding for students to pursue their MS and PhD in related topics (s. Educational Impact document for details)

Outlook • Although the funding for EUCLOCK ends with December 2010, the EUCLIS will be

maintained through the continued hosting by the Max Planck Society Computin Center and

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• the expressed intention of the European Biological Rhythms Society (EBRS) to contribute a small amount to its maintenance and incremental development

4.1.10 theWeP (Worldwide Experimental

Platform, Nov 2007-present) Project description The WeP builds on the very successful Internet-based application MCTQ (Munich ChronoType Questionnaire) and widens it to a platform for biomedical and epidemiological web-based studies. A first version developed by UP Diliman researchers and students has been released early this month. This version will also be used for the planned PhilSHIFT project (s. below). Collaboration Partners: Phase 1: Till Roenneberg (LMU), Serge Daan, Martha Merrow (University of Groningen, Netherlands), Russell Foster (Oxford University, UK) Phase 2: EUCLOCK (funding through EUCLIS) Impact Assessment: • A paper submission will be made to an ISI journal towards the end of the year when the first year

of wide use has been completed. 4.1.11 DOPA-SYS (Modeling the dopamine system in neurons, April 08 - present) Project description: This project resulted from my contacts and collaboration with a group of

clinical psychiatrists and neuroscientists in the Munich region. This group has organized an annual workshop called “International Workshop on Computational Neuropsychiatry (IWCN)” since 2005 (one of the founding members was Arvid

Carlsson, Nobel Prize winner in 2000). I have participated actively in the research of this group and have published a number of papers in the journal “Pharmacopsychiatry” (Impact Facto = 3.4). I am particularly interested in modeling the dopamine synapse, which plays an important role in various mental disorders such as schizophrenia, Parkinson’s disease, depression, etc. I hence suggested to Betty Dulam-Banawa in mid-2008 that for her thesis, she should work on integrating the recent models of the dopaminergic pre- and postsynapses. Dr. Alberto Main-Sanguino (Max Planck Institute of Biochemistry), who is working as a Postdoctoral Fellow, is with me, is also involved in mentoring her. Collaboration Partners: In addition to the co-organizers of the next (6th) IWCN – see Announcement Poster – and Alberto Marin-Sanguino, Eberhard Voit (Georgia Tech) and Seville Detera-Wadleigh are my main collaborators. Impact assessment:

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• The one-year PCASTRD sandwich scholarship for Betty Dulam-Banawa (Nov 2008-Oct 2009) was quite productive and she presented preliminary results in a poster at a Young Researchers’ Workshop at Ohio State University in August 2009. It is expected that Betty finish her PhD work by Sept 2010.

• A first joint ISI publication with Betty and Alberto will appear in Pharmacopsychiatry in May 2010.

• A further PhD advisee, Angelyn Lao, is currently modeling Alzheimer’s disease at the University of Rostock – she expects to finish and return to the Philippines in about year’s time and resume a teaching position at DLSU Manila

Outlook: • There is a reasonable chance by mid-2011 of forming a small group of young researchers

(B. Dulam-Banawa, A. Lao and R. Gabud-nee Santos) interested in Computational Neuroscience/-Psychiatry which can work with experimental/clinical groups at UP Manila and PGH. I am currently trying to establish the contacts to the latter as part of my BalikScientis work

• A pioneering book “Systems Biology in Psychiatric Research” that I have co-edited will be published this year. This graduate-level collection of essays will be helpful to set up trainings & courses as basis for widening Pinoy research in this field

• Many new connections between the circadian system and mental disorders are being discovered (eg a mutation in the CLOCK gene causes manic-like behaviour in mice) so that the chronobiological expertise from EUCLIS and related projects will also be helpful in this regard.

4.1.12 DOPA-KID (The dopamine system in the kidney, March 09 - present) Project description:

This project resulted from a discussion with Perdo Jose in April 2008 when we both attended (as BalikScientists) the HUGO Asia Pacific Conference in Mactan. I told him that I was working on modeling the dopamine system in the brain, whereupon he explained to me the importance of the same system in regulating salt-mediated hypertension. Discussions via email and a visit to his lab at the Children’s National Medical Center in March 2009 has led to a small 2-year NIH grant (April 2010 – Mar 2012) for the collaboration.

4. 4. ModelingModeling thethe dopaminedopamine systemsystem in in nephronsnephrons•• Joint Joint ExperimenterExperimenter --ModelerModeler

projectproject withwi th P. Jose (P. Jose (ChildrenChildren‘‘ssNational National MedicalMedical Center, Center, Washington DC), P. Naval Washington DC), P. Naval (UPD), E. Rodriguez (UA&P)(UPD), E. Rodriguez (UA&P)

•• ÍÍdeadea (HUGO AP Apr 08), (HUGO AP Apr 08), FollowFollow Up (Mar 09), NIH Up (Mar 09), NIH grantgrantobtainedobtained ((OctOct 09), 09), workwork just just initiatedinitiated

•• NephronNephron partsparts–– RenalRenal corpusclecorpuscle: : filtersfilters large large

solutessolutes–– RenalRenal tubuletubule: : reabsorptionreabsorption and and

secretionsecretion (of (of smallsmall solutessolutes))•• RenalRenal tubuletubule partsparts::

–– ProximalProximal tubuletubule–– LoopLoop of of HenleHenle ((descendingdescending, ,

ascendingascending))–– DistalDistal convolutedconvoluted tubuletubule

Collaboration Partners: s. slide above Impact assessment: since the project is just starting, I would like to defer the impact assessment Outlook: if successful, this would the first computational model of the dopamine system in the kidney 4.1.13 GWAPO (Genome Wide Association studies and Pathway Organization, March 09 - present) – Collaboration with IRRI on drought resistance trait of rice (March 2010 – present)

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Project description: The ideas which led to this project originated from discussions with Seville Detera-Wadleigh (NIH Bethesda, Maryland), who invited me to give a talk at CINP 2008. The integration of information from population-based studies (such as GWAS) with “omics” data in order to infer gene regulatory networks is a central challenge in today’s life sciences. Various authors have coined the word “systems genetics” for this approach (s. diagram from While our common original and longer term interest is to apply such methods to complex diseases such as bipolar disorder, we defined as a tractable first step (for a PhD thesis) to apply this to a complex genetic trait such as pigmentation. Jan-Michael Yap started to work on this in the third quarter of 2009. The method he studied was the one proposed by E. Schadt et al. (previously connected with Pfizer) and successfully applied to metabolic diseases. Unfortunately, it has been difficult to obtain all the data required to apply the method to the pigmentation trait. Hence, only recently, a collaboration with IRRI was initiated to apply various inference methods and possibly Schadt’s technique to various forms of perturbation-resistance (eg salt, drought,..) of rice. Besides the Schadt method, two other inference approaches will be used and compared. Eventually, this could lead to application in the C4 Rice Project, when similar data has been generated there. Collaboration Partners: S. Detera-Wadleigh (NIH Bethesda), R. Mauleon (IRRI) Impact assessment: project on rice has just started Outlook: a solution in this particular case will provide useful learnings for other similar applications. 4.1.14 HANAPIN-SM (Oct 08 – present) Project description and collaborators are discussed in Section . Impact assessment at UP Diliman: • PhD thesis work of Mrs. Riza Batista-Navarro has been started (this will completed at the

University of Manchester under an ERDT scholarship, which started in Sept 2009) • UPD OVCRD-funded project led by R. Batista-Navarro (co-investigator is Dr. G. Concepcion) to

provide the domain expert knowledge (4 research assistants, Apr 2009-Mar 2010) • MS Computer Science thesis of Kevin Manansala nearing completion (target Feb 2010) • Paper on “Towards an Ontology for Natural Products” by K. Manansala, R. Batista-Navarro and

E. Mendoza presented at the 6th Natural Language Processing Symposium at DLSU Manila on Sept 25

Outlook • Target release for NPO Release 1.0 is late March 2010, already favourable interest and comments

from international experts • Publications in international journals planned for Q1 or Q2 2010 • The ontology will be used as a basis for HANAPIN-SM, HANAPIN-SP and the information

system being developed at UPLB 4.1.15 PHOTO-PSOR (Optimal UV-Phototherapy of Psoriasis, July 09 - presemt) Project description: My interest in studying the epidermal melanin unit (EMU) also originated in the presence of dopamine in melanin synthesis. The current project however still doesn’t take the intracellular aspects, but remains on the lever of tissue modeling, specifically of cell types (including keratinocytes and melanocygtes in the EMU) which play a part in psoriaris, a prevalent kind of inflammation. Arjay Cayetano, who attended my

11

class on multi-agent systems, actually came up with the idea to build an agent-based model in order to study optimization opportunities for UV-Phototherapy for psoriasis. Thru Sally Vios of the UP Manila RIDO (Research Coordination Office), we have now established a collaboration with F. Roa and colleagues in the Dermatology Department of PGH. Collaboration Partners: F. Roa (PGH Dermatology Dept), P. Naval (UP Diliman, Dept of Computer Science) Impact assessment: • Interesting insights, especially for the typical combined therapy used in clinics, have been

gained through the current work • I am confident that we can get an international publication based on this (especially after

further validation with data available from PGH) Outlook:

The important role of neuromelanin, especially its protective functions which similar to epidermal melanin, in dopaminergic neurons of the substancia nigra have been established in the past decade. Recent results showing the presence of neuromelanin in many other parts of the brain have hightened my interest in studying this system in the near future.

MysteriousMysterious MelaninMelanin•• StudyStudy thethe dopaminedopamine subsystemsubsystem in in

thethe epidermalepidermal melaninmelanin uni tunit–– DopamineDopamine rolerole in in melaninmelanin synthesissynthesis–– Similarit ies/differencesSimilarities/differences withwith partsparts of of

thethe synapticsynaptic systemsystem !!–– InterestingInterest ing datadata forfor UV UV radiat ionradiation as as

perturbationperturbation•• ParticularlyParticularly interestinginteresting:: the

neuromelanin connection– Last 10 years: protective role of

neuromelanin in dopaminergicneurons (in substantia nigra) uncovered

• Binds toxic metals• Removes toxic intermediates• Scavenges reactive oxygen species

– Zecca et al (Nov 08):• New melanic pigments found in

putamen, cortex, cerebellum and other major parts of the brain

• Similar protective function•• MS MS CompComp SciSci thesisthesis byby Arjay Arjay

Cayetano on optimal UV Cayetano on optimal UV phototherapyphototherapy of of psoriasispsoriasis((collaborationcollaboration withwith F. Roa, PGH F. Roa, PGH DermatologyDermatology DeptDept))

4.1.16 VIRHO-BRANE (Modeling viral infection with branes, March 08 - ) Project description: This project’s goal is to use algorithmic systems biology approaches to understand virus-host interactions, specifically that of influenza A. Work began in the MS thesis of Pam David, which she defended in March 2008. A close collaboration with Johnrob Bantang (who was Postdoctoral Fellow at LMU Munich April 08 till Oct 09) led to the invention of the brane calculus PABM (Projective Activate Bud and Mate), which has already resulted in 2 international publications. Further work is being carried out to relate this too to the new theory of bigraphs (and biographical reactive systems): initial results have been applied to elucidate a current controversy between experimental groups regarding the number of hematogultinin (HA) trimers involved in endosomal escape of influenza A (paper in preparation). Applications to predictive modelling of non-viral gene delivery are also being studied (building on another recent ISI publication). Two new PhD students, Wilson Tan and Joseph Elias Co, have joined the team and will develop software platforms for scalable execution of virus-host interactions. Collaboration Partners: Johnrob Bantang (NIP UP Diliman), Susanne Bailer (LMU Medicine), Joachim Rädler (LMU Physics), Udo Reichl (MPI Magdeburg), Raul Destura (NIH Institute of Molecular Biology and Biotechnology) Al/ExAl/Ex´́ss PromisePromise (s) (s)

Impact assessment: (Nature, Nov 27, 2009) (Nature, Nov 27, 2009)

(May 2009)(May 2009)

• Interesting applications in non-viral gene transfer as well as the aforementioned analysis of influenza A endosomal escape indicate the potential of such algorithmic systems biology approaches

• Initial steps to move to 3D algorithmic modelling have been taken in Projects 4.1.7 (TOPOGEO) an 4.1.16 (MIMeMP)

(Aug 2009)(Aug 2009)

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Outlook: • The slide on right gives a glimpse of the fast growing interest in Algorithmic/Executable

Systems Biology approaches 4.1.17 MIMeMP (Mathematics and Informatics of Membrane-Mediated Processes)

Proposal Preparation (Sept – Nov 2009) Project description The proposal to a call by EU FP7 HEALTH-2010 was coordinated by E. Mendoza and addresses the scalable modeling of many critical membrane-mediated processes with a combination of recent results in Mathematics (3-dimensional topology and geometry) with innovative approaches in Informatics/Computer Science. This group of methods and tools, which is being termed “Membrane Informatics” forms an advanced approach in Algorithmic (or Executable) Systems Biology(cf. the News Feature “Biological Logic” in the Nov 27, 2009 issue of the Nature journal for details). The proposal preparation was supported with 30 000 Euros by the German Ministry for Research and Education. Fidel Nemenzo (Institute of Mathematics ) and Johnrob Bantang (National Institute of Physics) were able to participate actively in the preparation of the proposal. The proposal itself totals 3 million Euros and was submitted on Nov 19, 2009, with a decision expected in May/June 2010. Collaboration Partners:

Participant Number

Participant Organization Name Country

1 (Coord.) Ludwig Maximilians University Munich Germany 2 CAS-MPG Partner Institute for Computational

Biology, Shanghai China

3 University of the Philippines Diliman, Quezon City

Philippines

4 Computer and Automation Research Institute of the Hungarian Academy of Sciences, Budapest

Hungary

5 Alexandru Ioan Cuza University, Iasi Romania 6 University College Dublin Ireland 7 University of Sevilla Spain 8 University of Bologna Italy 9 Moscow State University Russia

10 Belarusian State University, Minsk Belarus 11 University of Udine Italy

Impact assessment: • While the final evaluation of the scientific value of the proposal is still pending, the

presentation of the ideas behind the proposal at an invited talk at the Max Planck Institute of Mathematics in the Sciences in Leipzig, Germany and the favourable feedback received confirms the potential of the methods proposed

Outlook: none yet (proposal stage) 4.1.18 ChronoInfo Mining (Oct 06 – present)

Project description: This project consists mainly of the research being done on data mining of circadian rhythmic patterns by Roselyn Gabud (nee Santos) for her in PhD Informatics at LMU. She is using a data set generated by J. Ricken on Neurospora crassa at the LMU Center for

Chronobiology. In addition, she is looking at novel quantitative measurements of the

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circadian system’s robustness, which can be derived directly from time series data (in particular without the use of a mathematical model). Collaboration Partners: H.P. Kriegel and team (LMU Informatics), T. Roenneberg, J. Diegmann (LMU Medical School) Impact assessment: • Poster presented at the European Biological Rhythms Society (Strasbourg, France, Aug

09) received good feedback Outlook: • The research work is targeted to finish by Q1 2011. 4.1.19 MINA (Models Integration of Networks of Apoptosis, Feb 2010 – present) Project description: This project continues (revives) previous work by Ric del Rosario and myself and was motivated by the proposal of Giselle Concepcion to publish the MS thesis work of Glory Ranches on HPDG (Heptylprodigiosin). The immediate goal is to provide a (probably simpler) Petri net model of a combined HPDG-mediated and cephalostatin-1 mediated apoptosis network and do structural and modular analysis. In a second step, partial results on kinetics of both pathways will be explored to develop a more complete kinetic model Collaboration Partners: Giselle Concepcion (MSI), R. del Rosario (GIS), Eva Rodriguez (UA&P) Impact assessment: none yet (project has just begun) Outlook: The work could be extend to cover similar work done by S. Jacinto’s lab at UPD IB. 4.1.20 HYPEN (Modeling with Hybrid PEtri Nets) Project description: Large and complex biological systems often need to be modelled with a combination of qualitative and quantitative methods. These hybrid models, though quite popular in engineering disciplines, are only slowly being used in systems biology. The framework of Petri nets offers a flexible conceptual basis for such approaches and need to be supported with functionally rich and openly available tools. Currently only Cell Illustrator (marketed by Fujitsu) is available for such modeling. The group of Monika Heiner at BTU Cottbus, Germany has embarked on an effort to extend their popular SNOOPY software to fill this gap and we have agreed to support this effort. A first step is Lowilton Mirasol’s activities in his MS Thesis to use efficient algebraic methods to solve related systems of equations. Collaborators: Monika Heiner (BTU Cottbus) Impact Assessment: although this project is just starting, given the expected growth in poularity of hybrid modeling, an openly available tool such as SNOOPY would be a great contribution to the research community (e.g. our recommendation to use Petri nets and canonical models in hybrid models in neuropsychiatry). Outlook: s. above 4.1.21 HALOReg (Modelin(g gene regulation in Halobacterium salinarum, Jan 2006 -

present) Project description: This project covers important gene regulatory modules in the halophile Halobacterium salinarum, and comprises the third important collaboration area-after metabolism and bioenergetics—with the Oesterhelt Lab at MPI Biochemistry. If forms part of the PhD thesis in Chemical Engineering of Locedie Mansueto under a Max Planck scholarship.

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Collaboration partners: Dieter Oesterhelt (MPI Biochemistry), Udo Reichl (MPI Dynamics of Complex Technical Systems, Magdeburg, Germany) Impact assessment: these results will represent the first computational models of essential regulatory modules in the organism. Outlook: The research is targeted to finish by December 2010. 4.1.22 New Initiatives (initiated within the current visit) • Lecture and brainstorming meeting on March 3 with faculty members of the Institute of

Biology (UP Diliman) o Z. Dasiao: modeling fish scales under particular perturbations o S. Jacinto: extension of the MINA work to the particular substances and cells that

she and a PhD student are working on o L. Argayosa: in collaboration with the Energy Development Corporation,

scientists at UPD are starting to study the biodiversity of organisms in extreme alkaline environments near geothermal energy sources. Previous work done with MPI Biochemistry on the halo-alkaliphile Natromonas pharaonis (paper by Gonzalez et al on the genome scale metabolic network reconstruction has been accepted at PLoS Computational Biology) will be helpful in answering a number of important questions of organisms found there.

• Potential FP7 participation of faculty members of the Institute of Chemistry (briefing on March 3) for the calls on ENV (ironment) and Energy

• Lecture and discussions with NIMBB faculty on March 8 4.2 Research Conferences (Co-Organized) 4.2.1 10th International Conference on Molecular Systems Biology (Feb 25-28, 2008) The 10th International Conference on Molecular Systems Biology (ICMSB 2008), one of the established events in the field, organized by the UPD Department of Computer Science (H. Adorna, J. Caro and P. Naval) and competently supported by UP ITTC, was a big success and hence a fitting celebration of the achievements of the first 5 years of SMILES☺ as well as a contribution to UP’s Centennial Year. It highlighted progress in Filipino research in Computational Systems Biology (first authors of 35% of papers presented were Filipnos) and established closer contacts with leading researchers such as A. Friedman (Ohio State University), E. Voit (Georgia Tech), M. Tomita (Keio University) A. Dress (PICB Shanghai) and O. Wolkenhauer, Rostock University) as well as other Asian scientists in the field. 4.2.2 1st Manila Shiftwork and Health Symposium (Manila, July 31, 2009) The first symposium brought to the attention of Filipino researchers and students recent scientific accomplishments that will impact the health and productivity of shift workers in the fast growing call center and BPO industry in the Philippines. This research builds on the work done in the ClockWork project (funded by the Daimler-Benz Foundation) which seeks to use the newest chronobiological findings (esp. individuality of the biological clock) to provide approaches and tools to manage shift schedules and work environment to maximize productivity and minimize health risks. Projects in Germany were done with Siemens and Mercedes Benz, but primarily in the factory environment. Conducting such a project will not only be beneficial to Filipino call center workers and companies but also provide new research insights. Around 70 persons participated, the keynote was given by Prof. Till Roenneberg of LMU Munich. A MOA was signed between LMU Munich and UP Manila to provide the foundation for fruitful long-term collaboration.

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5. Talks on BSB at important Conferences/Events in the Philippines 5.1 Scientific Societies in the Philippines 5.1.1 Annual Meeting of the Mathematical Society of the Philippines (May 2002)

• Mathematics of RNA Structures, Invited Talk at the Annual Meeting of the Mathematical Society of the Philippines, May 2002, Quezon City

5.1.2 Philippine Computing Science Conferences (2004, 2005, 2006, 2008) • Computational Aspects of Systems Biology, Invited Paper, Proceedings of 4th Philippine

Computing Science Congress (PCSC 2004), Feb 2004, Los Baños • Modelling biological systems with Petri Nets, Invited Paper, Proceedings of the 5th Philippine

Computing Science Congress (PCSC 2005), Mar 4-5, 2005, Cebu City • EUCLIS – An Information System for Circadian Systems Biology, Invited Paper, Proceedings

of the 6th Philippine Computing Science Congress (PCSC 2006), Mar 28-29, 2006, Quezon City

• Systems Biology of viral infection, Invited Paper, Proceedings of the 8th Philippine Computing Science Congress (PCSC 2008), Feb 23-24, 2008, Quezon City

5.1.3 NAST Round Table on Nanotechnology (Oct 2006) • Research Opportunities in Nanobiotechnology and Nanomedicine. Invited discussion input.

5.1.4 24th Annual Meeting of the Samahang Pisika ng Pilipinas (Davao, Oct 2006) • Systems Biophysics: An Opportunity for Filipino Researchers, Invited Paper, Proceedings of

the 24th SPP Physics Congress, October 25-27, 2006, Davao City 5.1.5 9th NIH Anniversary Research Forum (Feb 2007)

• Systems Biology in Medical Research. Keynote talk 5.1.6 35th Annual Meeting of the Philippine Society for Biochemistry and Molecular

Biology (Dec 2008) • The Impact of Systems Biology on Drug Discovery and Development. Keynote speech, 35th

Annual Convention of the Philippine Society for Biochemistry and Molecular Biology, Dec 1-2, 2008, Quezon City, Philippines.

5.1.7 NAST Annual Scientific Meeting (July 2009) • Social Jet Lag, Shift Work and Senior Citizens: New Insights into the Human Circadian

System, NAST Annual Scientific Meeting, July 8-9, 2009, Manila 5.2 Talks on BSB at International Conferences in the Philippines 5.2.1 2nd IEEE HNICEM Conference (Manila, Mar 2005)

• Growing interdisciplinary science & emerging technologies through communities of practice, Proceedings of IEEE HNICEM05, March 17-20, 2005, Manila

5.2.2 1st ENGAGE Conference (Manila, Mar 2006) • Digital Library Aspects in EUCLIS, 1st ENGAGE European Union-Southeast Asia ICT

Research Collaboration Conference, March 29-31, 2006, Manila 5.2.3 International Algebra and Combinatorics Conference (Quezon City, Apr 2006)

• Knot and Link Complements in the 3-Sphere: where Algebra and Combinatorics Meet Topology, Geometry and Arithmetic

5.2.4 MODEL 2007 (Boracay, Feb 2007) • Circadian Clocks: Bridges between Life and Environment

5.2.5 APAMS 2007 (Manila, Feb 2007) • SMILES: The First 4 Years, Proceedings of the 27th Annual PAASE Meeting & Symposium

(APAMS 2007), Feb 2007, Manila • Novel software approaches for Circadian Systems Biology, Proceedings of the 27th Annual

PAASE Meeting & Symposium (APAMS 2007), Feb 2007, Manila 5.2.6 10th ICMSB 2008 (Quezon City, Feb 2008)

• Systems Biology with SMILES, Keynote Speech, 10th International Conference on Molecular Systems Biology, Feb 25-28, 2008, Manila

5.2.7 1st International ICT4Health Symposium (Quezon City, Mar 2008)

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• Weaving the WeP- a worldwide experimental platform for Biomedical Studies, Invited Paper, International Conference on ICT4Health, March 2008, Quezon City

5.2.8 HUGO Asia Pacific Conference (Mactan, April 2008) • Understanding eukaryotic chemotaxis, Invited paper, 7th HUGO Asia Pacific Conference,

April 2-5, 2008, Cebu City, Philippines 5.2.9 APAMS 2009 (Quezon City, 2009)

• The Philippine Network for Bioinformatics and Systems Biology: Evolving a sustainable platform for integrating experimental and computational Life Sciences, 29th APAMS, July 13-15, 2009 Manila

• Modeling concurrent systems: from cell phones to cell membranes, 29th APAMS, July 13-15, 2009

5.2.10 10th Philippine Computing Science Congress (Davao City, 2010) • Geometric modeling of biological processes, Proceedings of the 10th PCSC, Davao

City, March 5-7, 2010

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6. Educational Impact of Activities in Bioinformatics and Systems Biology (BSB) Jan 2003 – present Establishment of Bioinformatics & Systems Biology tracks in the Math and Computer Sciences Graduate Studies Programs (MS/PhD) Individual graduate courses were incrementally introduced at the Mathematics Department (now Institute of Mathematics) starting in the second semester of AY 2002-2003. In addition, multi-disciplinary Lecture Series were conducted regularly to update and broaden the awareness of mathematical and computational applications in the Life and Environmental Sciences. The graduate courses MATH 235 (Mathematical Models in Population Biology) and MATH 236 (Mathematics in Biological Processes) are now offered annually. In addition, MATH 298 courses on Selected Topics in Systems Biology are offered regularly. At the Department of Computer Science, at least one CS 297 course per semester focuses on Computational Systems Biology. An entirely new course CS 297 “Introduction to Systems Biology in Practice” was prototyped and successfully in 2nd Semester AY 2007-2008 attracted 16 MS students, half of them experimentalists from MBB and MSI, enabling the forming of JEMPs (Joint Experimenter-Modeler Pairs) and execution of corresponding activities. The course was overall a success, and the results of a careful evaluation of the students’ feedback is being implemented in the course currently offered (9 graduate students). UP Diliman: PhD graduates

• Prospero Naval, Jr. (Electrical Engineering)Sept 2007 • Eva Rodriguez (Mathematics) Mar 2008 • Cherryl Talaue (Mathematics) Jan 2009

MS Math graduates: Rowena Yap (2006), Philip Zuñiga (2007), Phillip Ganir (2007), Alva Balbuena (2009), MS Computer Science O. Gonzalez (2004), J.M.Yap (2005), M.P. David (2008), M. Echavez (2008) C. Clarin (2008), R. Batista (2008) Current PhD students:

• Betty Dulam-Banawa (Mathematics): exp. graduation Sept 2010 • Jan Michael Yap (Electrical Engineering/ Computer Science) exp. Graduation Dec 2011 • Angelyn Lao (Mathematics): exp. Graduation Dec 2011 • Joseph Co (Mathematics), just starting • Wilson Tan (Bioprocess Engineering) to apply for DAAD scholarship, Fall 2010

Current MS students: • Lowilton Mirasol (Mathematics), Arjay Cayetano (Computer Science), Kevin Manansala (Computer

Science) UP graduates now on PhD studies/cholatships abroad (with my help):

• Orland Gonzalez, PhD Computer Science (LMU Munich) Max Planck scholar (Apr 2005-Jan 2009) graduated Jan 2009

• Locedie Mansueto, PhD Chemical Engineering (Magdeburg University), due to graduate Dec 2010 • Florence Balagtas-Fernandez, PhD Computer Science (LMU Munich, DAAD scholar Oct 2007-Sept

2010) due to graduate Sept 2010 • Roselyn Santos, PhD Computer Science (LMU Munich, EU scholarship Oct 2006-Dec 2010) • Pam David, PhD Biophysics (LMU Munich, DAAD scholar Oct 2008-Sept 2011, due to graduate Sept

2011) • Riza Theresa Batista-Navarro, PhD Computer Science, University of Manchester, ERDT Scholar Sept

2009-Aug 2012) UP graduates whom I helped obtain Postdoctoral Fellowships

• C. Monterola (Physics, Max Planck Fellowship, 2003-2005) • R.C. del Rosario (Math, Max Planck Fellowship, 2005-2008) • J. Bantang (Physics, Max Planck Fellowship, 2007-2009) • E. Juanico (Physics, Humboldt Fellowship, 2009-2011)

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Courses offered at UP Diliman since January 2003: AY 2002-2003:

• 2nd Sem: taught (together with Prof. V. Monje) a course MBB 197 Introduction to Mathematical and Computational Biology to 41 senior students at MBB. Two of those students, Carlo Lapid and Pamela David are currently pursuing PhD studies in Bioinformatics and Systems Biology (at WSU St. Louis, USA and LMU Munich, Germany) respectively.

• 2nd Sem: MATH 298 Research Topics in Mathematical and Computational Biology to 9 graduate students and faculty members

AY 2003-2004:

• 2nd Sem: MATH 298 Introduction to Algebraic Geometry and Computational Applications in Biology (team-teaching with F. Nemenzo)

• 2nd Semester: MATH 298 Introduction to Mathematical Modeling and Computational Applications (team-teaching with R. C. del Rosario)

There were 10-12 participants in each course. AY 2004-2005: 1st Sem:

• Participated in team-teaching with 8 lectures (focus: Canonical Modeling) (as part of the “Mathematical Biology 1

• Organized Research Lecture Series on “Mathematical Life Sciences” 2nd Sem:

• Participated in team-teaching with 5 lectures (focus: models of the cell cycle) as part of the “Mathematical Biology II Offering.

• I also conducted a 2-week block course on “Mathematical Biology” at UP Baguio (Feb 2005) AY 2005-2006: 1st Sem:

• Participated in team-teaching with 4 lectures (focus on Canonical models) as part of the “Mathematical Biology I” Offering

• Participated in team-teaching a new course on “Digital Geometry and Biological Imaging I” • Gave a lecture as part of the “Biological Structures” course at MSI

2nd Sem: • Participated in team-teaching with 4 lectures (focus on “Modeling circadian Systems”) as part

of the “Mathematical Biology II Offering. • Participated in team-teaching with 2 lectures in CS297 course “Qualitative modeling of

biological systems” • Participated in team-teaching with 8 lectures in MATH 298 course “Digital Geometry and

Biological Imaging II” • In addition, I offered a “Course on Systems Biology” (4 Saturday mornings) with an

attendance between 25-35 participants from various universities in Metro Manila. AY 2006-2007: 1 Sem:

• Starting with this semester, the Mathematical Biology courses could be offered independently by UPD Math faculty, in particular Prof. Escaner and Prof. Sy. My team-teaching approach contributed to this.

• Participated in team-teaching a course on “Digital Geometry and Biological Imaging I” 2nd Sem: AY 2007-2008: 1st Sem:

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• Starting with the 2nd Half of 2007, due to the availability of a dedicated DSL connection at UPD Computer Science, I was able to offer courses by Skype videoconferences. The course MA 235 “Mathematical Biology 1” was the first such course (6 lectures in July/August 2007).

2nd Sem: • CS 297: Introduction to Systems Biology (16 graduate students from Math, Computer

Science, Biology and Marine Science) AY 2008-2009: 1st Sem:

• CS 295 Introduction to Multi-Agent Systems and Applications in Systems Biology 2nd Sem:

• Introduction to Game Theory and Applications (offering did not materialize due to lack of registered students)

AY 2009-2010: 1st Sem:

• MATH 298: Petri Nets: Mathematical Theory and Applications (11 Math and Computer Science students participated)

2nd Sem: • CS 297: Introduction to Systems Biology (6 grad students from Math, Computer Science and

Engineering participate, with 3-4 sit-ins additionally) Current Status at UP Diliman • MS Math track for Math Biology is established; two base courses MATH 235, 236 offered

regularly; 2 PhD Math and ~10 MS Math graduates • CS 297 has offered „Intro to Systems Biology“ course twice (AY 0708, AY 0910 2ns

Sem); strong Systems Biology interest: 1 PhD EE graduate, 2 PhD Comp Sci candidates, ~ 10 MSCS graduates

• Bioinformatics offered regularly(?) at MBB • No computational courses offered as yet at IB (Meeting on Feb 19) • Would recommend a similar approach as at UPLB: tandem offering, slowly build a BSB

track for MS Biology majors DLSU Manila As already mentioned, Dr. Mendoza had started the manpower and research development activities on his own initiative in 2003. He gave two graduate courses at DLSU Manila (still under the auspices of the Math Department) in 1st quarter 2003 and 1st Quarter 2005. Results were: • Around 15 Computer science researchers (faculty and graduate students) received training

in Computational Systems Biology in those courses • 2 PhD scholarships in Systems Biology were obtained for DLSU Faculty (studies

ongoing) o Elaine Chua – DAAD scholarship for PhD Computer Science at the TU Munich,

her topic is “Building an Ontology and Models for Chronobiology”) o Angelyn Lao – scholarship at the University of Rostock for PhD Computer

Science with a topic on “Modeling Alzheimer’s disease” A Fulbright postdoctoral fellowship for Dr. B. Raposa at Virginia Bioinformatics Institute • A further PhD thesis (focussed on Systems Biology) ongoing: Mr. Rigan Ap-apid (Asst

Professor at DLSU College of Computer Studies) is now doing his PhD Computer Science thesis with Dr. Mendoza as thesis advisor. For this Dr. Mendoza has accepted an

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appointment as Adjunct Professor at DLSU CCS since January 2009. The target is for Mr. Ap-apid to finish his PhD by early 2011. The topic is “3D Geometric modeling of biological processes”.

UP Manila UP Manila MS Health Informatics Program The 3rd project which was targeted with the 1st BSP visit was an improvement of the MSHI program. Dr. Mendoza was already involved since 2005 in setting up the curriculum and supporting it for approval (among other things by DOST) and during his stay, he contributed to mentoring the first 2 MSHI graduates (with Bioinformatics focus). They also participated as sit-in’s in the CS 297 “Systems Biology in Practice” course that Dr. Mendoza offered at UP Diliman (2nd Semester, AY 2007-2008). He helped the MBaRC initiative formulate a proposal for improving the Internet communications structure which was submitted to PCHRD. Unfortunately, this proposal was approved, which made it difficult to implement the follow-on courses for MSHI and the programs of the other MBaRC participants. (Note that Dr. Mendoza since late 2006 has been able to regularly offer courses at UP Diliman, thanks to a dedicated DSL access at UPD Computer Science financed by the EUCLIS project). The follow-up on the MADMan and VirhoLex projects also suffered from the poor infracture situation, and it is a tribute to the patience and perseverance of the Manila teams that these two projects have resulted in the successes mentioned The following slides summarize the current status of the UP Manila MS program:

MSHI MSHI BioinformaticsBioinformaticsCoreCore CoursesCourses: 1st Semester : 1st Semester •• HI 201:HI 201: Health Health

InformaticsInformatics (( lecturelecture on on spectrumspectrum of of healthhealthinformationinformation domiansdomians in in thethe Phil Phil healthcarehealthcaresituationsituation, 3 , 3 unitsunits))

•• HI 271:HI 271: EthicalEthical and and SocialSocialIssuesIssues in Health in Health InformaticsInformatics (( lecturelecture on on issuesissues in in privacyprivacy, , confidentialityconfidentiality, and , and securitýsecuritý of of healthhealthinformationinformation, 1 , 1 unitunit))

CoreCore CoursesCourses: 2nd Semester: 2nd Semester•• HI 210: HI 210: Systems Analysis Systems Analysis

and Design in Health and Design in Health ((lecturelecture on on interactionsinteractionsbetweenbetween componentscomponents of a of a healthhealth informationinformation systemsystem, , 3 3 unitsunits))PrePre: HI 201: HI 201

•• HI 299: HI 299: Research Research methodsmethodsin Health in Health InformaticsInformatics((lecturelecture on on conceptsconcepts and and principlesprinciples of of researchresearch in in healthhealth informationinformationmanagementmanagement) )

2. 2. TheThe MS Health MS Health InformaticsInformatics Program at Program at UP Manila UP Manila (2005 (2005 –– presentpresent))

•• Joint Joint programprogram of CAS (MSHI of CAS (MSHI BioinformaticsBioinformatics Track) and CM Track) and CM (MSHI (MSHI MedicalMedical InformaticsInformaticstracktrack))

•• BeganBegan AY 2005AY 2005--0606•• BioinformaticsBioinformatics Track: Track:

–– MostlyMostly BS BS BiochemistryBiochemistrygraduatesgraduates

–– RecruitmentRecruitment difficultiesdifficulties despitedespiteDOST DOST scholarshipsscholarships

–– 3 3 graduatesgraduates so farso far–– CurrentlyCurrently 3 3 studentsstudents (1 in (1 in

second second yearyear , 2 in , 2 in firstfirst yearyear))

•• StructureStructure (in (in unitsunits):):–– 10: 10: CoreCore CoursesCourses–– 8 : Major 8 : Major CoursesCourses–– 6 : 6 : ElectivesElectives–– 6 : Thesis6 : Thesis

•• CurrentCurrent researchresearch focusfocus forfor MS MS thesisthesis–– InformaticsInformatics forfor biodiversitybiodiversity/ / naturalnatural

productsproducts ((fueledfueled byby DOST DOST pro jectprojectwithwith AteneoAteneo de de NagaNaga))

–– Info Info systemsystem on on virusvirus--hosthostinteractioninteraction ((VirhoLexVirhoLex))

–– My (My (recentrecent) ) recommendationrecommendation: : addadd„„MedicalMedical applicationsapplications of of chronobiologychronobiology““ as as furtherfurther focusfocus

MSHI MSHI BioinformaticsBioinformatics: Major : Major CoursesCoursesBNF 201: BNF 201: Fundamentals of Fundamentals of BioinformaticsBioinformatics (1)(1)BNF 216: BNF 216: Database Database modelingmodeling and and designdesign forfor

bioinformaticsbioinformatics (1+1)(1+1)BNF 231: BNF 231: ArchitectureArchitecture, , dynamicsdynamics and and

StructureStructure of of NucleicNucleic AcidsAcids and Proteins (3)and Proteins (3)BNF 240: BNF 240: RepresentationRepresentation and and AlgorithmsAlgorithms in in

BioinformaticsBioinformatics (3)(3)BNF 241: BNF 241: StochasticStochastic modelsmodels in in bioinformaticsbioinformatics

(3)(3)

MSHI MSHI BioinformaticsBioinformatics: : ElectivesElectives

BNF 242: BNF 242: DecisionDecision theorytheory in in bioinformaticsbioinformatics (1+1)(1+1)BNF 250: BNF 250: Business Business AspectsAspects of of bioinformaticsbioinformatics (2)(2)BNF 260: BNF 260: BioinformaticsBioinformatics in in clinicalclinical practicepractice (2)(2)BNF 232: BNF 232: MacromolecularMacromolecular ModelingModeling and and

ChemoinformaticsChemoinformatics (2)(2)BNF 233: BNF 233: AnalyticalAnalytical methodsmethods in in BioinformaticsBioinformatics (2)(2)BNF 234: BNF 234: ComputationalComputational Systems Biology (2)Systems Biology (2)

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New initiatives at UP Los Baños • Baltz Aguda‘s BSP visit revived interest (after my intermittent visits & talks since Aug

03) • Met Sept 16 with CAS Committee for new „Topics in Systems Biology“ graduate course

and finalized course description • First offering in AY10-11 First Semester by Baltz and myself (per Skype) with 3 persons

team-teaching with us • Audience will be multidisciplinary, but main group will be biologists (in contrast to

Diliman courses so far) • Complements the Bioinformatics course offered • Recommendation:

• Regular tandem offering (1st Sem Bioinformatics, 2nd Semester Systems Biology) • Extension to a program (MS track) first at MBB

ProBioSysProBioSys „„SkeletonSkeleton““ ProposalProposal V1.0 V1.0 forforMS Biology, MS Biology, BioinformaticsBioinformatics TrackTrack

BioinformaticsBioinformatics ((L+LabL+Lab)) Topics in Systems Topics in Systems Biology (L)Biology (L)

Research SeminarResearch Seminar•• BioinformaticsBioinformatics oror•• Systems BiologySystems Biology

YearYear 11

YearYear 22

Thesis Thesis BioinformaticsBioinformatics ororSystems BiologySystems Biology

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Appendix A Star Science articles (October 2007) on “Science with SMILES” Science with SMILES (Part 1 of 2) by Eduardo R. Mendoza On January 22 this year, two Filipinas addressed an international scientific meeting at Frauenchiemsee (near Munich, Germany) to a launch a novel information system called EUCLIS (EUCLOCK Information System). Just last month, IET Systems Biology, the pioneer journal dedicated to this new field (from the UK Institution of Engineering and Technology), published the paper “EUCLIS-An Information System for Circadian Systems Biology” and selected it as its “featured paper” (1). Of the five authors, two are the above mentioned recent MS graduates and another two are current MS students in Computer Science at UP Diliman. EUCLIS, a software system envisioned to evolve to a lasting information infrastructure for the worldwide chronobiology community, is designed and developed entirely at UP Diliman. It demonstrates that Filipino researchers and students already successfully engage in leading-edge work in the emerging field of computational systems biology.

What is novel about EUCLOCK and its information system EUCLIS? EUCLOCK, a research network of over 30 of the leading chronobiology laboratories in Europe, was launched in January 2006 with over 16 million Euros funding for 5 years. Chronobiology studies circadian clocks, which enable organisms to anticipate daily environmental changes by adjusting behaviour, physiology and gene regulation. The impact of such processes on health and quality of life in regulating sleep and well-being was described in a previous Star Science essay (2). The simulation of shift work for mice to investigate its long-term effects on health and a systematic study of the “light at night” theory (that exposure to light during sleep increases cancer risk) are two examples of highly relevant EUCLOCK research. EUCLIS (accessible at http://www.bioinfo.mpg.de/euclis ) supports this research by enabling geographical distributed teams to securely store and share experimental data and other important chronobiology information. such as annotated lists of relevant genes in different organisms and a library of over 14,000 chronobiology references. EUCLIS Version 1.5- to be released end of this month at the 16th European Chronobiology Summer School in Hungary-will go beyond enabling direct scientific collaboration and support community building through Clock Family Trees (an interactive documentation of the scientific genealogy of chronobiologists) and Clock Museum (an electronic collection of memorable chronobiology events).

EUCLIS is one of the current projects of the SMILES initiative at UP Diliman. SMILES (Statistics, Mathematics and Informatics in the Life and Environmental Sciences) was launched in March 2003 (then called “Mathematical and Computational Biology Initiative”) to enable interdisciplinary research in accelerating mathematical and computational approaches to understanding biological systems. Collaboration in SMILES is done consistently through Joint Experimenter-Modeler projects (JEMs). Though challenging-especially in the initial period as very differently trained specialists struggle to understand one another’s concepts and research philosophies-JEMs enable incrementally integrating increasingly quantitative experimentation and predictive modelling. In the EUCLIS project, the UP students work very closely with the team of Prof. Till Roenneberg at the Center for Chronobiology at the Ludwig-Maximilians-University in Munich (Germany) and other EUCLOCK researchers. In another SMILES project, MS students at UPD Computer Science worked closely with scientists at the International Rice Research Institute in Los Baños to develop components of the new information system for the Generation Challenge Program-2(GCP2). Mid-term focus on three specific areas is a further SMILES strategy in building sustainable research and education in Computational Systems Biology. Both EUCLIS and the GCP2 project are part of WINKS (Web-based INtegrated Knowledge-oriented Systems) and represent the more data integration-oriented research efforts in the field. The other two focus areas are DIMPLES (Digital IMage Processing in the Life and Environmental Sciences) and MOLES (Modeling NetwOrks in the Life and Environmental Sciences).

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Image processing has emerged has one of the key techniques for studying biological processes in living cells ( in vivo bioimaging). Fluorescent substances are attached to the cellular components of interest and careful analysis of the intensity changes allows the quantification of component amounts and location over time. These “time series” of data form the basis of quantitative models which allow the researchers to simulate and eventually predict new system characteristics to be verified by further experimentation. DIMPLES projects include a completed 2-year project of developing a Graphical Protocol Editor (an easy-to-use interface for planning and executing bioimaging experiments) for the innovative integrated microscopy system iMIC (Till Photonics, Germany) (3) and a current project for analyzing single cell gene expression in the context of synthetic gene delivery systems (LMU Physics). The planned Bioimaging Core Facility within the National Science Complex will enable collaboration with local experimental groups in this area in the future. The second part of this essay will report on Filipino progress in modeling biological networks- the key area of Computational Systems Biology. (1) Riza Theresa B. Batista, David B. Ramirez, Roselyn D. Santos, Maria Celeste I. del Rosario, Eduardo R. Mendoza: EUCLIS – An Information System for Circadian Systems Biology, IET Systems Biology, Vol. 1 No. 5, September 2007 (2) Cherry Mae G. Ignacio. Biological Clocks, Star Science 12/07/2006 (3) Philip Zuñiga, Alva Balbuena, Eduardo Mendoza: A Graphical Protocol Editor for an Integrated Microscopy System, Proceedings of the 5th ASEAN Microscopy Conference, Nov 24-25, 2005, Manila Science with SMILES (Part 2 of 2) By Eduardo R. Mendoza Modeling NetwOrks in the Life and Environmental Sciences (MOLES) For modeling biochemical networks, MOLES research focuses on methods which preserve the biological semantics and hence allow continued active project participation of the bioscientists. Petri Nets, for example, are very useful in formalizing qualitative aspects of networks, even when kinetic data for various components are unavailable. BST (Biochemical Systems Theory) or power law formalism has proven effective for constructing models concerned with average changes of system components over time, usually with coupled ordinary differential equations. These “canonical models” have only two kinds of kinetic parameters, which are easily interpreted biologically. The harder task of estimating such parameters from experimental data is rightfully assigned to the modeling partner, but the computational results are easily validated biologically by the experimenter. Parameter estimation for BST models—in the form of S-Systems or Generalized Mass Action (GMA) models—is a very active field of research, with over 25 original papers published in the last 4 years on the subject. The paper of Gonzalez et al (4) in “Bioinformatics” (the journal with the highest impact factor in the field) documents the successful SMILES collaboration of computer scientists at UPD and microbiologists at LMU Munich. The paper’s major contribution-the effective application of simulated annealing to parameter estimation-was verified using experimental data of the microbiologists on E.coli’s cadBA system. A more recent result of Filipino research (5) in this area is part of a growing collaboration with Prof. Eberhard Voit, a leading BST expert from Georgia Tech. The major part of this collaboration is the MAD (Munich-Atlanta-Diliman) initiative, which aims to build (in engineering terminology) a “problem solving environment” for Canonical Modeling by Bioscientists (CaMBio). An important activity towards the “problem solving environment” is a systematic benchmarking of available parameter estimation methods. Currently 4 UPD researchers and 5 graduate students are involved in this MAD Benchmarking project within SMILES.

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Education with SMILES From the very beginning, research and education for Computational Systems Biology have gone hand in hand in the SMILES initiative. These efforts over the last 4 ½ years have led to date not only to 5 ISI publications (4 published, 1 accepted) and 4-5 in preparation for submission in the next 6 months, but also to the establishment of specialization “tracks” within existing MS (Math, Computer Science) and PhD (Math) programs. 5 MS students (3 Math, 2 Computer Science) have finished and the first 2 PhDs are expected to graduate within the next 6 months. The annual “Biological Structures” course initiated at the Marine Science Institute by Giselle Concepcion and Ed Padlan has also contributed greatly to the students’ success, as it enabled non-biologists to get an overview of important concepts in modern biological research. A “Computational Systems Biology Group”, led by the labs of Henry Adorna and Prospero Naval was established in March 2007 to further advance research and graduate education at the Computer Science Department. Lessons from SMILES The first 4 1/2 years of SMILES have established a Filipino foothold in Computational Systems Biology. The insistence on tight integration of experimental and modeling work was the most important success factor. In this period, due to current lack of appropriate experimental resources in the country, most of the collaboration was done with groups abroad, particularly in Europe. The collaboration was nevertheless effective through the use of novel internet-based resources (Wikis, Skype videoconferences for project meetings) and organizational discipline (e.g. use of professional software development methodologies, goal-focussed meeting structures and follow-ups). In the future, I expect more local collaborations as appropriate infrastructure is built up e.g. in the National Science Complex. Further development of chip-oriented technology will dramatically drive costs of currently expensive equipment down, so that more quantitative experimental work can be done locally. The presence of knowledgeable computational partners will help in progressing serious systems biology research in the country. SMILES has also shown the feasibility of interdisciplinary research based on mutually-perceived value. To date, the initiative has not had to ask for any funding from Philippine sources. Many of the experimental groups abroad support the computational work through a Research Assistant Program (RAP), because they were impressed by initial results and the talent of the Filipino students involved. SMILES projects have led to 3 Max Planck Postdoctoral Fellowships and 4 PhD scholarships from various sources. SMILES is a “proof of concept”: similar initiatives will work for other institutions interested in computational life sciences. MBaRC (Manila Bay Research Corridor, pronounced “embark”), to be launched with DLSU Manila, UP Manila and Mapua in February 2008, will build on the lessons from SMILES. In the same month, SMILES celebrates its 5th anniversary as host of the 10th International Conference on Molecular Systems Biology (http://www.icsmb08.org ). (4) Orland R. Gonzalez, Christoph Küper, Kirsten Jung, Prospero C. Naval, Jr., Eduardo R. Mendoza, Parameter Estimation using Simulated Annealing for S-System Models of Biochemical Networks, Bioinformatics, Vol. 23, No. 4, February 2007 (5) Ricardo C.H. del Rosario, Eduardo R. Mendoza, Eberhard O. Voit, Challenges in Lin-log modeling of Glycolysis in Lactococcus lactis (accepted, under revision for IET Systems Biology)