Northwestern University Quantitative Biology Center (NUQuB)

Overview: Northwestern University Quantitative Biology Center (NUQuB); Richard Carthew; Northwestern University. The proposed NUQuB will transform our understanding of organismal growth and development through quantitative approaches. Observed biological processes during growth and development emerge from a complex interplay between genetic programming and extrinsic inputs. The revolution in ‘omics’ and high-throughput analysis has uncovered associations in the data, but the causal mechanisms remain unknown. The NUQuB will catalyze quantitative approaches at the intersection of mathematical sciences and biology that are essential to further the understanding of the biological mechanisms and principles. NUQuB consists of four interrelated research project areas that focus on different aspects of growth and development. Each project integrates mathematical approaches and advanced imaging, genomics, and metabolomics tools to explore biological processes across time, space, and extrinsic variables. The projects will uniquely combine three fundamental mathematical approaches: Dynamical systems theory; Stochastic processes; and Dimension reduction. NuQuB will engage students and investigators across this multi-disciplinary spectrum. The Center will conduct collaborative activities at the intersection of mathematical sciences and biology to spark innovation and sustain the field, including a visiting scholars program, a pilot project program, a science club learning module for K-12 education, workshops, and interdisciplinary training courses. The Center outputs will advance knowledge in the biological and mathematical sciences, generate new conceptual and mathematical models explaining biological processes observed in development and growth, and build cross-disciplinary capacity for future research in quantitative approaches. Intellectual Merit The proposed NuQuB Center represents a highly cross-disciplinary program for developing quantitative approaches to transform our understanding of the complex interplay between genetic programming and extrinsic inputs during organismal growth and development. The NuQuB will yield substantial technical advances in quantitative approaches including (1) new high dimensional biological datasets across spatial (cellular to organism) and temporal scales, (2) new conceptual models of diverse developmental processes, and (3) mathematical models that describe developmental emergence. Project 1 will yield single cell RNA sequencing data from a frog embryo and mouse embryonic stem cells at various stages during development and new conceptual models of embryogenesis using dynamic systems theory and statistical dimension reduction. The high dimensional approach and datasets from Project 2 will enable a new mathematical model of roundworm growth as a function of genotype and environmental variables. Project 3 will provide a new overarching conceptual model of oscillatory dynamics in the fruit fly and unique datasets that link molecular signatures in the fat body of the fly with phenotypic behavior every 2 hrs. The image analysis approach of Project 4 will study stochastic variation in fruit fly development and generate a new mathematical model of the impact of protein expression noise on development processes. Across projects new statistical methodologies and methods for combining multiple types of mathematical approaches will be tested and validated. Broader Impacts The proposed NuQuB Center will promote interdisciplinary education and workforce training at the intersection of mathematical sciences and