NewsletterAutumn 2009 Volume 5 Issue 1

The MBI receives major funding from the National Science Foundation Division of Mathematical Sciences and is supported by The Ohio State University.

The Mathematical Biosciences Institute adheres to the AA/EOE guidelines.

MBI EMphAsIs YEAr on MolEculAr IntErActIons WIthIn thE cEllnEtWork, scAlE, And coMplExItY

Biological processes can be characterized by different degrees of complexity at microscopic, mesoscopic and macroscopic levels. Historically, biological systems have been studied at different levels. However, experiments and theory now suggest that a more comprehensive approach is needed. this system approach requires col-laboration between experimentalists and theorists in the sciences, biosciences, and mathematical sciences. this emphasis year probes the systems approach to life within a cell.

For more information on the emphasis year program, please visit http://www.mbi.osu.edu/2009/scientific2009.html

cAll for ApplIcAtIons for MBI long-tErM VIsItors

MBI has openings for long-term visits from one month to one year for researchers in disciplines related to mathe-matical biology.

there are opportunities for research interactions with MBI postdocs, other MBI long-term visitors, the Ohio state re-search community, and participants in the many MBI sponsored events.

Upcoming scientific theme years are Evolution, Synchro-nization, and environmental Interactions: Insights from Plants and Insects (2010-11) and stochastics in Biological systems (2011-12). Non-thematic events include MBI-host-ed Current topic workshops, seminars, courses, and jour-nal clubs. Details may be found at http://mbi.osu.edu.

MBI accepts long-term visitor applications at all times. Please contact the MBI Director by mail or e-mail (sent to rebecca@mbi.osu.edu).

contEnts

upcoMIng Workshops ...............................................2

currEnt topIc Workshops ........................................4

spEcIAl progrAMs .......................................................6

long tErM VIsItors & postdocs ...............................8

MBI nEWs.......................................................................10

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upcoming WorkshopsWorkshop 3: sYnthEtIc BIologY(JAnuArY 25-29, 2010)

organizers: Jeff hasty and ron Weiss

synthetic biology is concerned with the design of genetic networks that perform desired functions in single cell and in multi-cellular environments. such synthetic circuits can be used to gain insight into the molecular components of gene regulation, thus reducing the complexity of gene regulatory networks of cells. This emerging field holds prom-ise for improved understanding of biological pro-cesses, and applications in varied areas such as programmed tissue engineering, biomaterial fab-rication, and biosensing.

the construction of de-novo genetic circuits be-gins with assembly of genetic components that regulate transcription, translation, phosphorila-tion, and synthesis of the response to signaling molecules in bacteria and in eukaryotes. these components are then assembled in various net-work topologies in a programmed fashion, which combines tools from nonlinear dynamics and sta-tistical physics with extensive array of techniques in traditional molecular biology.

the workshop will begin with foundational tech-nologies such as library parts, modules construc-tion and prediction. transcriptional networks with feedback and feedforward will then be present-ed. Applications will include engineering meta-bolic networks, cancer detection and therapy by engineered bacteria, biosensing, and energy production.

the workshop will bring together biologists, electri-cal engineers, and mathematical modelers. the mathematical tools will include network design, nonlinear dynamics, signal detection, and control theory.

Accepted speakers

Murat Acar (Caltech)J. Christopher Anderson (UC Berkeley)Adam Arkin (UC Berkeley)Calin Belta (Boston University)Kobi Benenson (Harvard University)Matthew Bennett (UC san Diego)Frederick Blattner (University of wisconsin-Madison)rob Carlson (Biodesic)James Collins (Boston University)Andy ellington (University of texas-Austin)Matthew Francis (UC Berkeley)timothy Gardner (Boston University)Jeff Hasty (UC san Diego)Homme Hellinga (Duke University)Clyde Hutchison (J. Craig Venter Institute)Mads Kaern (Ottawa Inst. of systems Biology)James liao (UC los Angeles)June Medford (Colorado state University)Alex Ninfa (University of Michigan)sven Panke (etH Zurich)Kristala Prather (MIt)John reinitz (stony Brook University)scott rifkin (UC san Diego)

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Workshop 4: InfErEncE In stochAstIc ModEls of sEquEncE EVolutIon(fEBruArY 22-26, 2010)

organizers: Ian holmes and gerton lunter

the past decade has witnessed the transition of computational biology, population genetics, and evolutionary biology, from relatively data-sparse and theory-driven subjects, into highly empiri-cal and data-driven disciplines. the continuing data-explosion has meant that descriptive studies have tended to outpace more in-depth theory development and statistical modeling. Neverthe-less, in the past decade our understanding of ge-nome and population biology and evolution has increased dramatically, and combined with the availability of data, it seems that the time is ripe to reap the benefits of these developments, by giving a new impetus to statistical modeling and theory development in computational biology, broadly defined.

In this workshop, we aim to bring together leading experts on genome biology and evolution, with an interest in quantitative modeling. we hope to create an interesting mix of, on the one hand, re-searchers whose main focus is on biology or evolu-tion, with researchers who are primarily interested in the modeling aspects of these biological prob-lems, from a mathematical, statistical, or algorith-mic perspective.

the program is organized around the following five interest areas:

Viruses and pathogensPaleogenetics and reconstructionGenome and pathway evolutionHuman diversity and populationsComparative genomics

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the workshop will feature about 20 short talks spread over five days, with plenty of time in between. In these slots it will be possible (and strongly encouraged) to organize informal breakout sessions in smaller groups, to discuss topical prob-lems in more depth.

Accepted speakers

Ana Arribas Gil (Universidad Carlos III de Madrid)steve Benner (University of Florida)elhanan Borenstein (stanford University)Graham Coop (UC, Davis)Daniel Falush (environmental research Inst.)Cedric Feschotte (University of texas-Arlington)robin Gutell (University of texas-Arlington)Asger Hobolth (MIt)Anna Kedzierska (Politechnical University of Catalonia)Carolin Kosiol (Inst. fur Populationsgenetik)David liberles (University of wyoming)rasmus Nielsen (UC Berkeley)Katie Pollard (UC san Francisco)tali raveh-sadka (weizmann Inst. of science)Adam siepel (Cornell University)Marc suchard (UC los Angeles)

For more information, please visit http://mbi.osu.edu/2009/ws4description.html

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This tree image was produced by Tom MacWright using the program “Context Free”.

Michael savageau (UC Davis)David schaffer (UC Berkeley)Michael simpson (Oak ridge National lab)Jingdong tian (Duke University)ron weiss (Princeton University)eckard wimmer (stony Brook University)erik winfree (Caltech)Yohei Yokobayashi (UC Davis)linchong You (Duke University)

For more information, please visit http://www.mbi.osu.edu/2009/ws3description.html

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current topic Workshops

BIofIlMs In InfEctIous dIsEAsE: BIologY to MAthEMAtIcAl ModEls And BAck AgAIn(MArch 22-25, 2010)

organizers: John gunn, dan Wozniak, and nick cogan

Biofilms are important in many human infections, particularly those involving indwelling devices. However, many non-indwelling device bacterial biofilms foster both acute and chronic infections, such as those in the lungs of cystic fibrosis patients, the gastrointestinal tract and hepatobiliary system, middle ear, and in the oral cavity. such infections often persist despite aggressive antimicrobial ther-apy and intact immunity. while bench experimen-tation has answered many questions about bio-films, such microbial communities are exceptional candidates for the application of mathematical modeling. These biofilms require nutrient cycling, are subjected to sheer forces, form on a variety of matrices, and are dynamic with organisms joining and exiting the biofilms. The molecular mecha-nisms underlying persistence are also of significant interest. these linked phenomena are applicable to mathematical models because they allow test-ing of hypothesis and can direct new experimen-tal efforts: a means to connect the different pro-cesses to each other and to weigh their relative contributions. this workshop aims to bring together modelers with bench scientists and clinicians work-ing on biofilm-involved human infections. Both sides will benefit dramatically from obtaining a better understanding of one other’s expertise and research directions, with the expectation of new research collaborations.

Accepted speakers

Nick Ashbolt (U.s. environmental Protection Agency)Bill Costerton (Allegheny-singer research Inst)David Davies (sUNY, Binghamton)Jack Dockery (Montana state University)Hermann eberl (University of Guelph)Mahmoud Ghannoum (University Hospitals

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2.6

2.8

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3.2

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Flux (

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The workshop focuses on the interaction between laboratory/clinical ex-perimentation and biofilm modeling. The aims are to explore and develop areas where experimentation can drive modeling which, in turn, can drive experimentation.

Case Medical Center)Kim lewis (Northeastern University)robert Palmer (NIH)Matt Parsek (University of washington)Karin sauer (Binghamton University)Martin schuster (Oregon state University)Hal smith (Arizona state University)Fitnat Yildiz (University of California, santa Cruz)

For more information, please visit http://www.mbi.osu.edu/2009/biodescription.html.

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MAthEMAtIcAl nEuroEndocrInologY(August 9-13, 2010)

organizers: richard Bertram, Arthur sherman, Mary lou Zeeman, gareth leng, and stanko stojilkovic

Neuroendocrinology is at the intersection of neu-roscience and endocrinology. Of the many endo-crine glands in the body, the one that is under the most direct neural control is the pituitary gland, which is located adjacent to the brain region called the hypothalamus. the anterior portion of the pituitary consists of several cell types, each of which is electrically excitable (like neurons) and which secretes a hormone when activated. Neu-rons within the hypothalamus act on pituitary cells to evoke hormone secretion at the proper times and under the proper physical stimuli. the pituitary hormones then act on other endocrine glands (like pineal, adrenal, ovaries, and testes) to influ-ence secretion of hormones. All of the hormones influence neuron activity within the hypothalamus,

Location of the pituitary gland in the human brain. Edited by Jim Thomas.

closing the loop. Mathematical neuroendocrinol-ogy is a new field that uses mathematical model-ing and analysis to help interpret neuroendocrine data and design new experiments. Models have been developed at the cellular and systems lev-el.

This workshop is the second in a series (the first was held at AIM) and will continue dialogues and col-laborations between mathematicians and experi-mentalists begun at AIM. One goal is to discuss problems in neuroendocrinology that can be ad-dressed using mathematics. these discussions took place during the first meeting, but we now have a better feel for the types of problems of interest. Another goal is to bring young mathematicians and experimentalists who have never worked with mathematical biologists into the mathematical bi-ology community to spur its growth.

For more information, please visit http://www.mbi.osu.edu/2009/mndescription.html

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special programsthE MBI colloquIuM

Larry Schlesinger, Division of Infectious Diseases and the Center for Microbial, Interface Biology, Director, Medical scientist program, OsUUnraveling the molecular events in the lung innate immune response to tuberculosisJanuary 4, 2010

Jian-Qiu Wu, Molecular Genetics, OsUMolecular Mechanism of Contractile-Ring Assem-bly in CytokinesisJanuary 11, 2010

De Witt Sumners, Mathematics, Florida state Uni-versityDNA TopologyFebruary 1, 2010

Joyce McLaughlin, Mathematical sciences, rens-selaer Polytechnic InstituteFebruary 8, 2010

Zena Werb, Anatomy, University of California, san FranciscoOf mice and women: How studying development gives us insights into cancerFebruary 15, 2010

Rafael Irizarry, Johns Hopkins Bloomberg school of Public HealthSome Statistical Issues in Measuring DNA Methyla-tionMarch 1, 2010

Michael Waterman, Biological sciences and Math-ematics, University of south CaliforniaReading DNA Sequences Along Eulerian PathsMarch 15, 2010

If you would like to view the talks live on the web, please email streaming@mbi.osu.edu and request a link.

upcoMIng puBlIc lEcturEs

Steven Strogatztheoretical and Applied Math-ematics, Cornell UniversityFebruary 16, 2010

Iain CouzinDepartment of ecology and evolutionary Biology, Princeton UniversityApril 28, 2010

MBI WIntEr quArtEr coursE: thE MAthEMAtIcs of chEMIcAl rEActIon nEtWorks

Instructor: Martin Feinberg (Chemical engineering and Mathematics, Ohio state University)

there is now quite a bit known about connections between reaction network structure and qualita-tive properties of the corresponding differential equations, especially when the reaction rates are described by classical mass action kinetics*. In fact, there are powerful theorems that permit deep inferences about qualitative behavior even when parameter values -- e.g., rate constants -- are unknown (the usual situation in biology). It is both fortunate and remarkable that the theorems themselves are easy to understand and easy to apply, even by those without extensive training in higher mathematics.

For more information regarding this course, please visit http://mbi.osu.edu/courses/winter2010.html.

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VIsItIng lEcturEr progrAM: BrIngIng undEr-rEprEsEntEd groups Into thE MAthEMAtIcAl BIoscIEncEs

MBI has established the Visiting lecture Program to sponsor visits of mathematical biologists to in-stitutions that have large numbers of undergradu-ate students who are members of groups that are under-represented in the mathematical sciences community. the purpose is to encourage mem-bers of these groups to go to graduate school and to develop careers in the mathematical biosci-ences. In addition to delivering a lecture on math-ematical biology that is accessible to an under-

Janet BestOhio state

Lisa Faucitulane University

Jonathan MattinglyDuke University

Emery BrownMIt

Marty GolubitskyOhio state

Asamoah NkwantaMorgan state

Erika CamachoArizona state

Christine HeitschGeorgia tech

Michael ReedDuke University

Carlos Castillo-ChavezArizona state

Fern HuntHoward and NIst

Miranda I. Teboh-Ewungkemlafayette College

Ricardo Corteztulane University

Trachette JacksonUniversity of Michigan

Talitha WashingtonUniversity of evansville

Isabel DarcyUniversity of Iowa

James KeenerUniversity of Utah

Abdul-Aziz YakubuHoward University

Lisette de PillisHarvey Mudd

Nancy KopellBoston University

graduate audience, the lecturers will meet with individual students and with groups of interested faculty and students. MBI will partially support the expenses of up to five VLP lecturers each year.

see http://www.mbi.osu.edu/about/vlprogram.html for more details. the following mathematical biologists have agreed to be lecturers in the MBI VlP program.

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long term Visitors & postdocsnEW long tErM VIsItors

fernando AntonelliFernando is an Associate Professor of Mathe-matics at Federal University of sao Paulo - Bra-zil (UNIFesP), and his research interests include nonlinear dynamics and bifurcations in equivari-ant and network dynamical systems, with appli-cations in neuro-sciences and gene regulatory

networks. Currently, Dr. Antoneli and his colleagues at the school of Medicine of the Federal University of sao Paulo (ePM-UNIFesP) are interested in stochastic dynamical sys-tems theory and its role in modeling noise in regulatory gene networks.

dieter ArmbrusterDieter Armbruster’s current research interests are to determine how the methodology used in industrial production systems can be applied to biological production systems. the emphasis is on three directions: (1) stochastic discrete event simulations treating enzymatic networks as fac-

tories; (2) dynamical systems and control approaches to the well known MAPKKK signal transduction pathway; and (3) a new project started at MBI to look develop a Chapman-enskog expansion for the Multiscale Models of Chemotaxis developed by Chuan Xue. the expectation is that such an approach will allow to deal with large gradients. In addition, we are going to study Chemotaxis within a flow and in finite domains.

lisle gibbsDr. lisle Gibbs is a Professor in the the Depart-ment of evolution, ecology and Organismal Biol-ogy at Ohio state University. He is an evolution-ary biologist who studies the molecular basis of adaptive variation in wild organisms using snake

venom proteins as his model system. while at the MBI he will apply statistical genetic techniques to model the rapid evo-lution of venom genes both within and between species.

david romanoDavid is working on coupled cell networks with Marty Golubitsky. He is looking forward to learn-ing about systems biology and neuroscience while at MBI.

Martin Wechselbergerthe aim of Martin’s research is to develop math-ematical tools to understand the underlying dy-namics of observed rhythms and patterns in the biosciences. His research develops new meth-ods within the framework of dynamical systems theory which (a) explain complex oscillatory

patterns observed in nonlinear systems and (b) identify geo-metric features of PDe models that give rise to wave pat-terns with sharp interfaces.

while visiting the MBI, he is focusing on two particular prob-lems: (a) pseudo-plateau bursting observed in pituitary lac-totroph cells and (b) tactically-driven cell migration patterns observed in wound healing. In both cases, an important fea-ture of the observed biological rhythm (a) and pattern (b) is that they evolve on multiple scales which is usually modeled by singularly perturbed systems. Identifying “canards” within such singularly perturbed systems is a key step to understand these patterns.

chang-hong WuChang-Hong’s research interests are applica-tions of partial differential equations and lattice dynamical systems to mathematical ecology and population genetics. He is mainly interest-ed in the front propagation in discrete media.

recently, he started working with Dr. Yuan lou on a PDe model and a non-local model arising in biology. He is inter-ested in understanding the difference between these mod-els.

Apply for a visit!

MBI has openings for long-term visits from one month to one year for researchers in disciplines related to mathematical biology.

there are opportunities for research interactions with MBI postdocs, other MBI long-term visitors, the Ohio state re-search community, and participants in the many MBI spon-sored events.

MBI accepts long-term visitor applications at all times. Please contact the MBI Director by mail or e-mail (sent to rebecca@mbi.osu.edu).

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ers at the University of Michigan wherein he will combine multi-scale modeling with model-driven experimentation to develop a comprehensive and predictive computational model that will aid in the characterization of At-101, a small molecule inhibitor of the anti-apoptotic members of the Bcl-family of proteins, as an anti-angiogenic and anti-cancer agent in the treatment of head and neck cancers. He also plans to collaborate with researchers at OsU and Notting-ham

suzanne robertsonsuzanne’s research interests are in the area of mathematical ecology and epidemiology. she received her PhD in Applied Mathematics from the University of Arizona under the direction of J. M. Cushing. Her thesis work focused on the spa-tial patterns formed by stage-structured species

as a result of density dependent dispersal between life-cycle stages. At the MBI, she is working with Joe tien (Mathemat-ics, OsU) on modeling the spatial spread of Cholera. she has also started working with Ian Hamilton (eeOB, OsU). they are looking at the role of disease in habitat selection.

rebecca tienrebecca is interested in mathematical and computational ecology with applications to population dynamics, management and con-servation of natural resources, particularly as they relate to aquatic ecology. she is currently working with elizabeth Marschall and Yuan lou

on the biomagnification of PCBs and other heavy metals and their potential effects on food web interactions and population dynamics in lake erie.

Yunjiao WangYunjiao works in the fields of nonlinear dynami-cal systems and system biology. Her recent re-search on nonlinear dynamical systems focuses on studying dynamics of networks, especially on studying general theory of coupled cell systems, functions of motifs, coupled oscillators and trans-

tivity of oscillations. Her current research on system biology focuses on studying heterochronic signaling pathways in C. elegans and nuclear factor \kappaB signaling pathways, especially its interaction with other signaling pathways in the cell and between cells.

kun ZhaoKun’s research interests are in the area of analy-sis and applications of nonlinear partial differ-ential equations (PDes) in various branches of science and engineering. In his Ph.D. thesis, he studied qualitative behavior of solutions to initial-boundary value problems for several systems of

nonlinear evolutionary partial differential equations arising from fluid dynamics and civil engineering. At MBI he is cur-rently working on several systems of PDes arising from math-ematical biology, namely, the Keller-siegel type chemotaxis models and the Cahn-Hilliard-Hele-shaw equations.

nEW postdocs

Erik Bloomquisterik is currently working with investigators in the College of Medicine and the College of Veteri-nary Medicine on the classification of biomark-ers for the detection of urological disease. In addition, he is working on a genetic epidemio-

logical study with investigators in the College of Medicine. In the autumn quarter, he taught a graduate course in the College of Public Health at Ohio state. In addition to his work at Ohio state, he is collaborating on an ancient DNA study with an investigator at Penn state, and is writing a review of phylogeography.

Julia chifmanJulia’s research primarily focuses on phylogenet-ic invariants and their performance under the coalescent process (joint work with collabora-tor and mentor laura Kubatko, OsU). Although much progress on phylogenetic invariants has previously been made for a single gene, it is well-

known that gene trees are not topologically equivalent with the species tree. By deriving phylogenetic invariants within the coalescent framework, her work extends their utility to the case of multi-gene data for which the goal is inference of the species-level phylogeny. she is also interested in the analysis of the mammalian iron metabolism using algebraic tools (joint work with Biosciences mentor reinhard lauben-bacher, Virginia tech).

shu daishu is interested in the PDes arising from math-ematical biology and physiology, bifurcation analysis and numerical analysis. Currently he is working on applied dynamical systems and mathematical cardiology.

Marisa EisenbergMarisa’s research focuses on building ODe models of neuroendocrine regulation and de-veloping methods to address identifiability and parameter estimation questions. Her disserta-tion research centered on building physiology-based feedback control system models of the

human hypothalamic-pituitary-thyroid axis, to address sev-eral clinical issues in thyroidology. she is extending this work in several new directions involving other hormone regulatory axes, circadian rhythms, and thyroid cancer. Marisa is also working on identifiability and parameter estimation of non-linear ODE models and exploring identifiability applications in phylogenetics.

harsh JainHarsh is interested in biochemically-motivated modeling of angiogenesis and cancer growth, and the simulation of novel therapies target-ing both cancer cells and tumor vasculature in order to evaluate their potential and aid in the design and execution of clinical trials of these

drugs. while at MBI, he will work on a project with research-

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mBi neWsfEAturEd InstItutE pArtnEr: MAthEMAtIcAl And coM-putAtIonAl BIologY At unIVErsItY of cAlIfornIA, Ir-VInE

recently, the biomedical community has emphasized the importance of mathematics as a critical enabling technology for the future of biology. this interplay be-tween mathematics and biology is resulting in new and challenging mathematical problems and a better under-standing of complex biological systems. such interactions have led to collaborations between mathematicians and biological scientists, and the development of mathemati-cal and computational biology (MCB) research groups at University of California at Irvine (UCI).

Collaborations between the mathematicians and biolo-gists that make up our MCB research cohort have been ongoing for the past eight years. this interdisciplinary re-search led to the creation of the Center for Complex Biol-ogy systems (CCBs) in 2002, which was awarded a grant in 2007 to establish a National Center of excellence in systems Biology by the NIH. the goal of the Center is to study complex biological systems using a multidisciplinary approach, with mathematics and computations as one of the critical tools. In 2005, UCI established the Center for Mathematical and Computational Biology (CMCB) in the school of Physical sciences. this Center emphasizes the role of mathematics in facilitating interdisciplinary re-search collaborations between biologists and mathema-ticians (pure and applied). the Center is also involved in the development of new mathematical and computa-tional tools that can be utilized in these interdisciplinary interactions.

there is a dynamic and exciting postdoctoral fellow train-ing program in MCB at UCI. Postdoctoral fellows have ample opportunity for close interaction with experimental biologists in addition to training activities in modern ap-plied and computational mathematics. Our research emphasizes on using interdisciplinary approach to bet-ter understand how simple biochemical and biophysical relationships among molecular and cellular components give rise to complex biological systems with an individual identity. Currently, there are twelve postdoctoral fellows and six faculty members at UCI Department of Mathe-matics in collaboration with a dozen of experimental bi-

ologists working on various research projects funded by NIH and NsF.

In addition to collaborative research, the cohort of MCB re-search faculty members initiated a series of interdisciplinary training activities for students. In 2005, MCB faculty in CCBs received a three-year award from the Howard Hughes Medical Institute (HHMI) to support the development of an interdisciplinary graduate training program to bring to bear mathematics and computation on biology. A Mathemati-cal, Computational and systems Biology (MCB) Gateway Graduate Program was officially established at UCI in 2007 as a broad training program involving five colleges at UCI with mathematicians playing leadership roles in the Pro-gram. In 2009, the Program received a NIH/NIBIB t32 grant to support the MCB graduate students in their first year at UCI. Currently, there are 14 first year graduate students in the MCB program, and around 30 Ph.D. graduate students in the Department of Mathematics working in MCB.

For more details on MCB research and training activities at UCI, please refer to the websites of CMCB (http://cmcb.math.uci.edu/), CCBs (http://ccbs.bio.uci.edu) and MCsB (http://mcsb.bio.uci.edu/), or contact Professor Qing Nie at qnie@math.uci.edu.

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fEAturEd MBI postdoc: JudY dAY

this edition of the MBI quarterly newsletter features an ar-ticle on MBI postdoctoral fellow Judy Day. Day completed her Ph.D. thesis in mathematics from the University of Pitts-burgh in 2007 under the direction of thesis advisor Jonathan rubin. In her thesis, Day addressed various mathematical approaches for understanding and controlling the inflam-matory response, and upon graduation, was interested in continuing research that uses mathematical concepts to respond to questions arising in immunology. In september of 2007, Day started as a postdoctoral fellow at the MBI and began meeting with Avner Friedman (OsU, Department of Mathematics) and larry schlesinger, M.D. (Director, Center for Microbial Interface Biology at OsU Medical Center). As a result of this initial dialogue, a project was formulated that focused on the role of lung macrophages in the host re-sponse to respiratory pathogens. In the lung, alternatively activated macrophages (AAM) form the first line of defense against microbial infection. Due to the non-inflammatory nature of AAM, the lung can be considered as an immunosuppressive organ for respiratory pathogens. However, as infection progresses in the lung, another population of macrophages, known as classically activated macrophages (CAM) enters. CAM are far more effective than AAM in clearing the microbial load, produc-ing pro-inflammatory cytokines and anti-microbial defense mechanisms necessary to mount an adequate immune re-sponse. Because AAM have been classified as non-inflam-matory macrophages, they could be one important cause for the delay in the lung’s protective immune response as reported in the literature. their research was concerned with determining the first time when the population of CAM becomes more dominant than the population of AAM. this proposed “switching time” may have important implication in vaccine and therapy development.

As a preliminary investigation into the concept of a “switch-ing time”, Day and colleagues sought to mathematical-ly model the host response of the lung to the intracellular pathogen, Mycobacterium tuberculosis. recently, their re-sults were published in the Proceedings of the National Acad-emy of sciences (PNAs) . they developed a mathematical model that describes the interactions among immune cells, bacteria populations (intracellular and extracellular), and cytokines (soluble proteins involved in cell signaling) in the context of a tuberculosis infection. the model, based on a system of differential equations, represents a useful tool to analyze strategies for reducing the switching time, and to generate hypotheses for experimental testing. Previous models of tuberculosis infection did not focus on the early stages of the infection, nor did they specifically consider the role of alternatively activated macrophages in the course of the infection.

the model predicted a switching time of 50 days. this du-ration corresponds well with the time it takes from initial ex-posure to Mtb to a positive skin test (6-12 weeks), which is indicative of a noticeable immune response. In addition, Day performed simulated experiments in order to shorten the switching time so that the more effective immune cells would enter the picture sooner in hopes of better contain-ing the infection. the results showed that the use of a par-ticular therapy did help reduce the switching time, and that this most often corresponded to reduced bacterial loads. A reduction in bacterial loads may imply a reduction in the duration of treatment of latent infection, the likelihood of re-activation, and the latent pool or resistant bacteria. How-ever, this therapy alone was not sufficient to eradicate the infection, a result that resonated with the literature describ-ing clinical trial outcome using this therapy. In addition, sen-sitivity analysis revealed that early signaling from the AAM is important in the development of protective immunity and that therapies should reduce bacterial loads but not at the expense of a reduction in signaling to downstream immune mediators.

this current work is the beginning of a larger aim envisioned by Day and collaborators, which is to understand the host response of the lung to a variety of airborne pathogens in addition to tuberculosis, such as anthrax and tularemia. Depending on the type of pathogen, the initial immune re-sponse of the lung can vary a great deal. For instance, M. tuberculosis is a host-adaptable microbe where both host and microbe can co-exist. On the other hand, anthrax in-halation is lethal to the host in a very short amount of time after initial exposure due to a potent immune response that overwhelms the host. the authors are currently preparing an opinion piece for the journal tuberculosis that will highlight the role of mathematical modeling and encourage collab-orations among mathematicians and experimentalists in the development of vaccinations and therapeutic strategies for combatting tuberculosis infection.

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MAtHeMAtICAl BIOsCIeNCes INstItUte

the mission of the MBI is:• to foster innovation in the development and applica-

tion of mathematical, statistical, and computational methods for the solution of significant problems in the biosciences;

• to engage mathematical and biological scientists in the solution of these problems; and

• to expand the community of scholars in mathematical biosciences through education, training, and support of students and researchers.

MAthEMAtIcAl BIoscIEncEs InstItutEthe Ohio state UniversityJennings Hall, 3rd Floor1735 Neil AvenueColumbus, OH 43210

Phone: 614-292-3648Fax: 614-247-6643http://mbi.osu.edu

If you would like us to include in-formation on upcoming meetings/pro-

grams or employment opportunities, please contact Yuan Lou at lou@math.ohio-state.edu.