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Annual Report for DMS-0931642 Year 2014-2015 and No-Cost Extension Year 2015-2016

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Annual Report for DMS-0931642 Year 2014-2015 and No-Cost Extension Year 2015-2016 Annual Report for DMS-0931642 Year 2014-2015 And No-Cost Extension Year 2015-2016 INTRODUCTION The Mathematical Biosciences Institute (MBI) is a multi‐disciplinary initiative that facilitates interaction between the mathematical sciences (which includes mathematics, statistics, and computational science) and the biosciences (which includes the biological sciences, medical sciences, and environmental sciences that relate to the living world). The Institute is devoted to the mathematical biosciences, which includes all areas of research in bioscience where participation of the mathematical sciences will lead to important progress. MBI offers a vigorous program of research and education, and fosters the growth of an international community of researchers in mathematical biology. The mission of MBI is: . To foster innovation in the application of mathematical, statistical, and computational methods in the resolution of significant problems in the biosciences . To foster the development of new areas in the mathematical sciences motivated by important questions in the biosciences . To engage mathematical and biological scientists in these pursuits . To expand the community of scholars in mathematical biosciences through education, training, and support of students and researchers. To support this mission, MBI programs are designed to reinforce and build upon existing research efforts in the mathematical biosciences, and to inspire and accelerate the expansion of the community and its intellectual growth. These include emphasis year programs, current topic workshops, education programs, and research projects. The administrative and governance structure of MBI are designed to support the mission of the Institute. MBI addressed the following scientific challenges in its programming during 2014‐2015: Need to learn the scientist’s language: In order to contribute to the solution of problems in the biosciences, mathematicians and statisticians must first learn some science. In particular, they must learn the bio‐scientist’s language before they can understand the problems clearly enough to bring the power of the mathematical sciences to bear. The continuing rapid pace of research in the biosciences precludes most active biomedical researchers from devoting substantial effort to learning additional mathematics. MBI actively encourages mathematical scientists to learn the bio‐scientists’ language, and to work with them in highly interdisciplinary teams working the boundaries of mathematics and science. Need to develop new mathematical/statistical models and techniques: While we can expect that established methods in mathematical science will be of immediate use, the quantitative analysis of fundamental problems in bioscience will require new ideas and new techniques. Similar observations apply to diverse research areas across the biosciences ranging from the study of basic structures in the brain to the expression, regulation, and control of genes. MBI is providing a forum for scientists to begin 1 modeling these systems in ways which are scientifically relevant yet amenable to analysis that requires skillful approximations and new techniques. Need to increase the community’s size: The current size of the mathematical bioscience community is relatively small when compared to the demands of life sciences. MBI encourages the participation of established mathematicians and statisticians in mathematical bioscience and continues to nurture new generations of researchers. MBI activities fall under five principal categories (scientific programs, postdoctoral fellows, national impact, education, and diversity) and MBI is developing new programs in each of these categories: workshops, institute partners and mentoring, early career awards and long‐term visitors, education programs, and diversity and outreach. The MBI directorate for 2014‐2015 included: Martin Golubitsky, Ph.D. (Principal Investigator and Institute Director); Tony Nance, Ph.D. (Deputy Director responsible for administering the postdoctoral program); Greg Rempala, Ph.D. (Deputy Director responsible for providing scientific advice and liaison to the workshop organizing committees); Helen Chamberlin, Ph. D. (Associate Director responsible for diversity issues); Laura Kubatko, Ph.D. (Co‐Principal Investigator and Associate Director responsible for the summer education programs); Janet Best, Ph.D. (Associate Director responsible for the summer graduate program); and Andrej Rotter, Ph.D. (Associate Director responsible for providing leadership for relations between MBI and the Ohio State University Medical Center and chair of the MBI Colloquium Committee). MBI had seven full‐time administrative staff members plus three student employees for 2014‐2015. The specific positions included: one Financial and Human Resources Manager (Nikki Betts); one Program Coordinator (Matthew Thompson); two Program Assistants (Will Gehring and Casey Jacobs); one Office Administrative Associate (Rebecca Martin); one Systems Manager (Michael Siroskey); one Web Applications Developer (Alex Kasler); and one Systems Specialist (Jason Bray). MBI had 20 postdoctoral fellows continuing or starting their program during 2013‐2014. They were Marcio Albasini Mourao, Noelle Beckman, Richard Buckalew, Josh Chang, Ruchira Datta, Kimberly Fessel, Jeff Gaither, Wenrui Hao, Karly Jacobsen, Jae Kyoung Kim, Kang‐Ling Liao, Leopold Matamba Messi, Jay Newby, Matt Oremland, Michael Schwemmer, Michal Seweryn, Leili Shahriyari, Lucy Spardy, Marc Sturrock, and Ying (Joy) Zhou. A. INFORMATION ON MBI PROGRAMS 1. MBI Emphasis Program: Cancer and Its Environment Cancer is one of the world's biggest killers. Cancer is initiated from cells with specific genetic mutations that cause them to lose control of proliferation. This loss of proliferative control, whilst necessary, is not sufficient to cause cancer; subsequent mutations and selection need to occur. Cancer is an evolutionary disease, where rounds of mutation and selection will drive the emergence of a tumor. The selection 2 pressures that a growing tumor encounters are manifold but can largely be classified as microenvironmental. The tumor microenvironment consists of the extracellular matrix, growth promoting and inhibiting factors, nutrients (including oxygen and glucose), chemokines, and importantly, other cell types including (but not limited to) fibroblasts, immune cells, endothelial cells and normal epithelial cells. In order for selection to operate properly there needs to be variation in the tumor population ‐ tumors are known to be genetically extremely heterogeneous. This genetic heterogeneity produces phenotypic heterogeneity in which individual tumor cells can have distinct phenotypic behaviors within the same tumor. As the tumor mass grows, so does the heterogeneity; eventually the mass becomes too large to be supported by nutrient diffusion alone, so some subset of the tumor population then becomes hypoxic. This hypoxia will eventually give way to cell death if nutrient levels continue to fall but the tumor has two ways to combat this problem. First it can begin to utilize a different nutrient source (e.g. glucose) by altering its metabolism and second it can initiate the process of angiogenesis from nearby vessels. The process of recruiting and growing a new vasculature, once fully realized, gives the tumor an almost limitless nutrient source and also a highway to other parts of the human body. Metastases are cells that successfully break away from the primary tumor and initiate new tumors at secondary sites. There can be many of these metastatic cancers at many different sites in the body and ultimately, for most patients, it is these cancers that cause death. There are hundreds of types of cancer, classified by the tissue from which they arise and by the type of cells involved. For example, leukemia is a cancer of white blood cells, carcinoma is a cancer originating from epithelial cells and glioma is cancer of the brain. There are also many ways to treat cancer, most of which start with surgery and end with chemotherapy and/or radiotherapy. In recent years we have seen the emergence of immunotherapies and molecularly targeted therapies. Immunotherapies exploit the immune system by either enriching or aiding its ability to attack the cancer. Molecularly targeted therapies exploit the fact that specific mutations are present in a large proportion of the cancer cells and block the activity of these mutations. Both of these new therapies have had differing degrees of success but, as in most treatments, failure is ultimately caused by the emergence of a resistant tumor population that tends to be more aggressive and less easy to treat. This brief overview illustrates the complex interactions at the molecular, cellular and tissue levels involved in the emergence and development of cancer, and emphasizes the need for mathematical models that synthesize a framework for understanding the existing phenomena and that make testable predictions as to how interventions will influence the outcome. Emphasis Program Organizing Committee MBI Emphasis Year on Cancer and Its Environment 2014‐2015 Organizing Committee Alexander Anderson (Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute) Rick Durrett (Department of Mathematics, Duke University) Mariam Eljanne (Physical Sciences‐Oncology, National Institutes of Health (NIH)) Avner Friedman (Department of Mathematics, The Ohio State University) Kirk Jordan (Data Centric Systems, IBM Corporation)
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