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Celebrating Women's History Month 2022 with Dr. Kanchana Ravichandran, Moderna

Event Type
Women Chemists Committee
Chem Annex 1024
Jun 1, 2022   2:00 pm  
Originating Calendar
Chemistry - Department Events

Lecture: Therapeutic enzyme engineering using a generative neural network

Dr. Kanchana Ravichandran:
A native of Chennai, India, Dr. Ravichandran obtained a PhD in Biological Chemistry from MIT where she studied mechanistic enzymology under the guidance of Dr. JoAnne Stubbe. Dr. Ravichandran is currently an Associate Director at Moderna, a pharmaceutical and biotechnology company dedicated to the discovery and development of messenger RNA medicines for patients. At Moderna, she leads the Protein Science group and works within Research and Early Development to manage protein production, assay development, antibody discovery and protein engineering required for the advancement of mRNA therapeutics. Dr. Ravichandran additionally holds bachelor’s degrees in Biology, Biochemistry and Neuroscience from Brandeis University.

Enhancing the potency of mRNA therapeutics is an important objective for treating rare diseases, since it may enable lower and less-frequent dosing. Enzyme engineering can increase potency of mRNA therapeutics by improving the expression, half-life, and catalytic efficiency of the mRNA-encoded enzymes. However, sequence space is incomprehensibly vast, and methods to map sequence to function (computationally or experimentally) are inaccurate or time-/labor-intensive. Here, we present a novel, broadly applicable engineering method that combines deep latent variable modeling of sequence co-evolution with automated protein library design and construction to rapidly identify metabolic enzyme variants that are both more thermally stable and more catalytically active. We apply this approach to improve the potency of ornithine transcarbamylase (OTC), a urea cycle enzyme for which loss of catalytic activity causes a rare but serious metabolic disease.

Question and answer session will follow at 3:30 p.m.

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