Cellular and molecular discoveries of pathogenesis
Basic Research

The Basic Research Section leverages and integrates the analytical, computational, and translational strengths of the DMPI to understand the regulatory architecture of complex biological systems in the context of health, disease, and aging.  The expertise in this section ranges from cellular and molecular biology to integrative animal physiology.  Cellular and animal models have been developed for pancreatic islet biology, mitochondrial biology, calcium signaling, immunology, insulin action, inter-organ crosstalk, exercise physiology, and whole body energy balance.  The overarching goal of the program is to provide new mechanistic understanding of basic cellular processes that can be exploited for prevention and treatment of disease.

The sophistication and capacity of modern biotechnology has shifted the landscape of basic life sciences research from that of traditional biological reductionism to a much more integrative, holistic systems approach.  It is now recognized that living organisms are not merely the sum of their parts, but rather, interactions among cellular components and their environment are ultimately responsible for form, function, and phenotype.  Implicit in this philosophy is that the failure of biological networks to maintain homeostasis gives rise to pathophysiology and the development of complex diseases.  The DMPI was founded on the principle that an understanding of these networks can be informed via the power of ‘omics technologies coupled with computational modeling methods that permit integration and interpretation of large, diverse data sets.  The goal of the Basic Science Section is to test, modify, and validate these interpretations by combining systems biology with integrative physiology using tractable model systems that allow rigorous evaluation of the spatial and temporal dynamics of cellular and physiological processes in living systems.   

Using knowledge gained from collaborations with the other four research sections of the DMPI, the scientists in the Basic Research Section are designing animal and cell-based experiments to uncover lesions in biological networks that contribute to metabolic dysfunction.  We aim to define critical regulatory nodes within these networks and gain novel insights into areas such as nutrient sensing, metabolic control, and disease pathogenesis.  Built on the conceptual framework of translational and retro-translational science, the structure of the DMPI provides unique opportunities to move discoveries from cell and animal research to the context of human disease and clinical trials and to use results of human studies to inspire new ideas for mechanistic research in model systems.  Ultimately, this research strategy is expected to guide innovative approaches to disease detection and personalized medicine aimed at monitoring and promoting metabolic health.

Recent studies from the Basic Science Research Section include the identification of potential new targets for activating β-cell proliferation (1), elucidation of the influence of dietary fatty acids on insulin sensitivity (2),  and the effects of obesity and lipid stress on mitochondrial function and glucose control (3).