More information can be found on the CSG website: http://csg.sas.upenn.edu
Junhyong Kim, PhD, Chair and Patricia M. Williams Professor of Biology in the School of Arts and Sciences, and James Eberwine, PhD, Elmer Holmes Bobst Professor of Systems Pharmacology and Translational Therapeutics in the Perelman School of Medicine, have been awarded a Centers of Excellence in Genomic Science (CEGS) program grant supported jointly by the National Human Genome Research Institute and the National Institute of Mental Health. Drs. Kim and Eberwine are leading a multi-disciplinary team developing new state of the art technologies to measure genomics elements at the scale of sub-cellular structures with this five-year, $10.5 million grant which is the first CEGS awarded to Penn.
A cell is a highly complex system with distributed molecular physiologies in structured sub-cellular compartments whose interplay with the nuclear genome determine the functional characteristics of the cell. A classic example of distributed genomic processes is found in neurons. Learning and memory requires modulation of individual synapses through RNA localization, localized translation, and localized metabolites such as those from dendritic mitochondria. Dendrites of neurons integrate distributed synaptic signals into both electrical and nuclear transcriptional response. Dysfunction of these distributed genomic functions in neurons can result in a broad spectrum of neuropsychiatric diseases such as bipolar and depressive disorders, autism, among others. Understanding these complex genomic interactions within a single cell requires new technologies including a nano-scale ability to make genome-wide measurements in localized compartments and to effect highly localized functional genomic manipulations, in cells in culture as well as in live tissues.
This NIH award will fund the creation of the Center for Sub-Cellular Genomics (CSG). The CSG’ mission is to develop many of these new technologies to enable the dissection of complex genomic interactions within a single cell. Specifically, CSG will be developing new methods to target DNA and RNA sampling at sub-cellular resolution in live cells; high-throughput isolation and microfluidics chemistry for sub-cellular fractions; sub-cellular resolution mass-spectrometry; and computational tools for analysis of sub-cellular genomics data. These technologies will be developed to permit multi-modal simultaneous measurement of these subcellular chemistries in the same cell.
The new technologies developed by CSG will be utilized to generate a comprehensive atlas of genomic signatures of sub-cellular compartments in the mammalian neuron system and more importantly to associate sub-cellular processes to cell function and dysfunction. In this age of personalized medicine, the ability to assess the genomics of single cells and their subcellular structures will provide the ultimate in patient specific therapeutics by facilitating patient selective and cell specific drug targeting. The technologies and neuron-focused data obtained here will be relevant to neurodegenerative and neuropsychiatric diseases including Schizophrenia, Depression, Autism Spectrum Disorder, Traumatic Brain Injury, and Alzheimer’s.
Kim and Eberwine are also Co-directors of the Penn Program in Single Cell Biology (PPSCB) and will leverage the PPSCB infrastructure to facilitate CSG’s efforts in disseminating, training, and carrying out outreach activities in sub-cellular genomics.
This is an interdisciplinary effort requiring experts in genomics, neurosurgery, neuroscience, nanotechnology, informatics, and mass spectrometry. Co-investigators involved in this project include Dr. Ron Anafi , Assistant Professor of Medicine, Perelman School of Medicine, Dr. M. Sean Grady , Charles Harrison Frazier Professor and Chairman of Neurosurgery, Perelman School of Medicine, Dr. David Issadore , Assistant Professor of Bioengineering and Electrical & Systems Engineering, Dr. Daeyeon Lee , Professor of Chemical and Biomolecular Engineering, Dr. Jai-Yoon Sul , Research Associate Professor of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, Dr. Jonathan V. Sweedler , James Eiszner Family Chair of Chemistry and Director of the School of Chemical Sciences, University of Illinois, Dr. John A Wolf , Assistant Professor of Neurosurgery, Perelman School of Medicine, and Dr. James Y. Zou , Assistant Professor, Stanford University.