Multiscale regulatory networks in the mammalian brain: integrating genes and physiology

Brainstem circuits play a key role in the maintenance of autonomic homeostasis. Maladaptation of these control systems underlies development and progression of chronic diseases such as hypertension. Understanding the network processes driving adaptation, plasticity, variability and robustness of these control circuits is important in developing targeted and personalized therapeutics.

We have focused on unraveling and integrating the brainstem regulatory networks at multiple scales including cell-cell interactions and intracellular processes spanning signaling, transcriptional and post-transcriptional regulation, and electrophysiology. In probing these functional networks, we need to be able to assay and manipulate molecular processes occurring in individual cells on a very large scale of sample numbers and types, in their tissue and phenotypical context, to support network reconstruction. These requirements/approaches are uncommon in present mammalian systems biology practice and require synthesis of novel technical approaches into a coherent resource.

I will outline our strategy and present the results from our recent high-throughput experiments and computational modeling as first steps in reaching this goal. Importantly, our analysis thus far revealed a dynamic landscape of cell phenotypes and several network processes underpinning the robustness/plasticity of function in the brainstem.

About Rajanikanth Vadigepalli

Dr. Vadigepalli is an Associate Professor of Pathology, Cell Biology and Anatomy at Thomas Jefferson University. He also holds an Adjunct Professor position in Chemical Engineering at the University of Delaware. He received his Bachelors in Chemical Engineering from the Indian Institute of Technology in Madras, India, in 1996; his PhD in Chemical Engineering from the University of Delaware in 2001, with Specialization in Systems and Control Engineering; and his postdoctoral training in Bioinformatics at Thomas Jefferson University.