Molecular Decryption of Immune Responses

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Event details

Date 16.04.2018
Hour 12:15
Speaker Prof. Sai Reddy, ETH, Basel (CH)
Location
Category Conferences - Seminars
BIOENGINEERING SEMINAR
(sandwiches will be served)

Abstract:
The ability to predict and correspondingly manipulate antibody responses is highly valuable for biotechnology and medicine. To achieve this requires a greater molecular understanding of antigen selection and specificity in antibody repertoires. In this presentation I will describe how we are decrypting antibody repertoires by identifying antigen-associated molecular patterns. Detection of these patterns is based on the principle of convergent selection: different individuals exposed to the same antigen respond with antibodies that converge to similar sequence space. Molecular convergence is specifically identified by bioinformatic recoding of high-throughput sequencing data of antibody repertoires into constituent biochemical sequence space. By combining this approach with a statistical learning framework we are able to accurately predict antigen exposure and potential antigen specificity based on antibody sequences alone.
 
I will also highlight recent work in our group aimed towards engineering antibodies at high-throughput in mammalian cells through genome editing. We have recently established a technique known as homology-directed mutagenesis (HDM), which is able to generate mutagenesis libraries directly in mammalian cells using CRISPR-Cas9. HDM enables several of the most essential methods of antibody engineering, which are usually only possible in microbial or in vitro systems (e.g., phage, yeast), to be performed in directly in mammalian cells. This includes generation and screening of synthetic libraries for antibody discovery and affinity maturation. Finally, by combining HDM with high-throughput sequencing, we are able to perform deep mutational scanning on antibodies in order to decrypt their antigen-recognition sequence landscape.

Bio:
Sai Reddy is a tenure-track Assistant Professor in the Department of Biosystems Science & Engineering, ETH Zurich, Switzerland. His research group uses methods in systems and synthetic biology to study and manipulate immune responses for applications in biotechnology, vaccination, and immunotherapy. Sai Reddy holds B.S. (2003) and M.S. (2004) in Biomedical Engineering from Northwestern University (Evanston, IL, USA). He completed his Ph.D. thesis at Ecole Polytechnique Fédérale de Lausanne (EPFL, Switzerland) in Bioengineering and Biotechnology (2008).  Sai Reddy did post-doctoral research at the University of Texas, Austin (2008-2011).

 

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