Brown University Center for Computational Molecular Biology

Events

CCMB Seminar Series 2002-2003

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Center for Computational Molecular Biology Seminar Series

Predicting CNS Permeability

Joanne Yeh
Department of Molecular Biology, Cell Biology and Biochemistry at Brown University

Abstract:
Accurately predicting the ability of a molecule to enter the central nervous system (CNS) through the blood brain barrier (BBB) would be an extremely useful tool for designing drug compounds. Designing drugs for targets in the CNS is a difficult task because of the presence of the blood brain barrier. The BBB is a selective membrane that prevents small molecules from entering the CNS, making drugs that are effective in other parts of the body virtually useless for CNS targets. As a preliminary step to designing more useful drugs that can act on targets in the CNS, we are developing a methodology for predicting the permeability and ultimately, the bioavailability, of different classes of molecules into the CNS. While there are in-vitro assays to measure the log blood-brain permeation coefficient, these methods are expensive, time consuming, and not very practical when screening large libraries of potential molecules. Hence, the ability to predict blood brain barrier permeability will be an enormous help in designing drugs that target the CNS. Our results (Doniger, Hoffman, and Yeh (2003) Journal of Computational Biology, 9(6): 849-864) with two artificial intelligence approaches will be reported.

Wednesday, March 12, 2003
4:00 pm
McMillan Hall, Room 115

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From Genome to Vaccine: Epitope Mapping and Vaccine Design Tools

Annie DeGroot
Bio Med Community Health, Brown University, and EpiVax

Abstract:
The high mutation rate of many pathogens and restriction of T cell response to epitopes due to HLA polymorphism has significantly hindered the development of efficient epitope-based or "epitope-driven" vaccines. Bioinformatics tools such as EpiMatrix and Conservatrix, which search for unique or multi-HLA-restricted (promiscuous) T cell epitopes and can find epitopes that are conserved across variant strains of the same pathogen, have accelerated the process of epitope mapping. Additional tools for screening epitopes for similarity to "self" (BlastiMer) and to assemble putative epitopes into strings if they overlap (EpiAssembler) have been developed at EpiVax. Tools that map proteasome cleavage sites are in development. These bioinformatics tools offer a significant advantage over the "overlapping" or "exhaustive" method of epitope selection because high throughput screening is performed in silico, followed by confirmatory studies in vitro. Epitopes discovered using these tools are being used to develop novel vaccines and therapeutics for the prevention and treatment of infectious diseases such as HIV, hepatitis C, tuberculosis, and some cancers. More recent applications involve deriving novel vaccine candidates directly from whole genomes, an approach that has been named "genome to vaccine".

Wednesday, March 5, 2003
4:00 pm
McMillan Hall, Room 115

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