A Reactor Model of Endoplasmic Reticulum to Investigate Protein Folding Diseases

Dr. Santiago Schnell
The University of Michigan Medical School

11am Friday, October 26, 2012
EB3105


Abstract:
The endoplasmic reticulum (ER) play fundamentals role in the folding of newly synthesized proteins and in degrading damaged proteins to regulate cellular protein homeostasis.  Failures in normal protein homeostasis lead to increased protein damage that may, in turn, contribute to a variety of protein-based diseases, including diabetes, cancer, cataracts, Alzheimer's disease and Parkinsons disease. In this talk, we present a reactor model of  protein processing in the ER which we have used to investigate how the protein folding disease phenotype can be manifested.  We found that the onset and rescue from a protein folding disease can be controlled by some combination of the transition time of proteins in the ER, the ratio of wild-type and mutant proteins inflow rates in the ER and a chemical interaction parameter between wild-type and mutant proteins. Our model results present new research strategies that may ameliorate protein folding diseases.

Bio:
Dr. Santiago Schnell is interested in investigating biochemical and cellular physiology systems comprising many interacting components, where modeling and theory may aid in the identification of the key mechanisms underlying the behavior of the system as a whole. Dr. Schnell is Associate Professor of Molecular & Integrative Physiology and Computational Medicine & Bioinformatics at the University of Michigan Medical School. He is also a Brehm Investigator at the Michigan Comprehensive Diabetes Center.  He received a M.Sc. in Biology from Universidad Simón Bolívar (Venezuela) and then a doctorate in Mathematical Biology from the University of Oxford (United Kingdom), respectively. Dr. Schnell held two prestigious research positions at the University of Oxford between 2002‐2004: Junior Research Fellow at Christ Church (a college of Oxford) and Senior Research Fellow of the Wellcome Trust at the Centre for Mathematical Biology. Between 2004‐2008, he was Associate Director of the Biocomplexity Institute at Indiana University. He serves in the editorial boards of EIT Systems Biology, Computational Biology & Chemistry, Mathematical Biosciences and Biomath.  Dr. Schnell is permanent member of the NIH Modeling and Analysis of Biological Systems Study Section.  He received the 21st Century Scientist Award from the James S. McDonnell Foundation, and he is an elected Fellow of the Royal Society of Chemistry.

Hosts:

Dr. Betty HC Cheng (CSE)
Dr. Christina Chan (CHEMS)