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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