Faculty of Engineering and Natural Sciences
Modeling toxic Alzheimer Amyloid ion channels
Dr. Ruth Nussinov
Department of Human Genetics, School of Medicine, Tel Aviv University
While there is a general agreement that Alzheimer toxicity results from calcium leakage into the cell, the mechanism of amyloid toxicity is poorly understood. There are two schools of thought in this hotly debated field: the first favors membrane destabilization by intermediate to large amyloid oligomers, with consequent membrane thinning and non-specific ion leakage; the second favors ion-specific permeable channels lined by small amyloid oligomers. Confusingly, published results currently support both mechanisms. Thus, currently available structural and physiological data present a challenge for computational biology: Can computations provide candidate models consistent with the experimental data and assist in reconciling the two views?
The talk will review current views of amyloid toxicity, highlighting mechanistic insights which might be obtained by combining experiment with detailed modeling. It will further describe our on-going work on the modeling of the Alzheimer A-beta oligomers in solution and in the lipid bilayer, and illustrate consistency with currently available experimental data. The modeling has been carried out using detailed atomistic molecular dynamic simulations and experimental data.
Short CV: Dr. Ruth Nussinov is a Professor in the Department of Human Genetics, School of Medicine, Tel Aviv University, and a Senior Principal Scientist and a Senior Principal Investigator at the National Cancer Institute (USA). She has received her B. Sc degree in Microbiology from the University of Washington (Seattle, Washington) and her Ph.D in Biochemistry from Rutgers University (N. J.). She was a Fellow at the Weizmann Institute, and a visiting scientist at the Chemistry Department at Berkeley and at the Biochemistry Department at Harvard. Currently her research focuses on computational studies of protein-protein interactions, protein folding, binding, amyloid formation, conformation and toxicity; and functional dynamics. Her research is inter-disciplinary, with a strong component of computer science. Dr. Nussinov serves on a number of Editorial Boards of Journals; is the Editor of several books. She is a frequent invited speaker at National and International meetings, Colloquia and seminars; has organized meetings and sessions; an elected member of the Council of the Biophysical Society, serves on steering committees and has fulfilled various roles in the academic community.
Wednesday, 5 December 2007 at 13:40, FENS G032