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“Systems Analysis of Glycosylated Antibodies: Regulation, Engineering and Functions”
Sephideh Dolatshahi, Ph.D.*
Postdoctoral Associate
Department of Biological Engineering
Massachusetts Institute of Technology
Wednesday, January 23, 2019
10:00 a.m. – 11:00 a.m.
Health and Sciences Research Building, E160
Videoconference
Georgia Tech: Whitaker Bldg 3115; TEP, stream from your PC (no conf. room)
https://bluejeans.com/809850842
ABSTRACT
N-linked glycosylation is a post-translational modification that affects potency, safety, immunogenicity, immune effecto functions, and clearance of various classes of therapeutic proteins including antibodies. These modifications are shaped by cellular and enzyme-mediated processes, regulated at both transcriptional and metabolic levels. Understanding how these processes operate dynamically will be vital to designing the most effective therapeutics for various treatment applications, but at the present time principled insights are limited due to the complexity of contributing factors. I will describe a systems biology approach that includes multi-dimensional omics analyses and mathematical modeling to develop a mechanistic understanding of N-glycosylation of antibodies produced during fed-batch cultures of producer cells, generating new insights that offer opportunities for more precise control of N-glycosylation. The functional role of glycosylation will then be probed in a representative study, where selective transfer of antibodies with di-galactosylated Fc-glycan profiles across the placenta from mothers to newborns is observed. This additional work can provide critical information for the design of next generation maternal vaccines that can be engineered to elicit antibodies giving enhanced immunity in neonates.
BIOGRAPHY
Sepideh Dolatshahi is a Postdoctoral Fellow, working with Prof. Doug Lauffenburger in the Department of Biological Engineering at MIT. She received her Ph.D. in 2015 from Georgia Institute of Technology under the supervision of Prof. Eberhard Voit, where she developed advanced methodologies for the modeling of metabolic pathway systems based on time series data. Her primary research interests are systems biology of immune regulation and immunotherapies, and inter-species translation of cellular processes in animals to those in humans.
Host: Hee Cheol Cho
