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SYNTHETIC POLYPEPTIDES DISRUPT FIBRIL FORMATION IN NEURODEGENERATIVE DISEASES (NDD)
Prof. Uri Raviv: Department of Physical Chemistry, Hebrew University, Jerusalem
"This grant helped me to establish my collaboration with Prof. Deming, through which I have been able to design and obtain unique synthetic peptide that are not commercially available, and study their effects on the self-assembly of β-A (amyloid-beta) peptides."
Prof. Timothy Deming: Department of Bioengineering, UCLA
"This grant helped me establish a research connection with Prof. Raviv to study self- assembly of our polymers, which would not have been possible otherwise."
Certain proteins, polypeptides and biopolymers found in brain tissues, such as β-A (amyloid-beta), are capable of self-assembly and aggregation to form fibrils. Such aggregates blocking nerve cell activity are associated with various NDD (Neurodegenerative Diseases), including AD (Alzheimer’s Disease), and prion, Huntington and Kennedy diseases.
Profs. Raviv and Deming focus on the rational design of peptides to disrupt these NDD-related processes. In the long run, this might lead to new therapeutic approaches for treating a broad range of NDD and other conditions.
Cooperation This BSF grant allows the efficient combination of synthetic capabilities of Prof. Deming's group with studies on the structure and interactions between the novel synthetic polypeptides and aggregating proteins, carried out in Prof. Raviv's laboratory. Such characterization greatly improves the rational design of synthetic polypeptides. Prof. Deming’s team is now preparing a variety of diblock copolypeptides with a solubilizing (polylysine) and aggregating (such as polyvaline or polyalanine) domains.
Findings Profs. Raviv and Deming’s project has three main aims: 1. The rational design of synthetic polypeptides to disrupt and control the self-assembly and aggregation of biopolymers and proteins, such as β-A. 2. Devising polypeptides to modify the chemical nature of the exposed part of the aggregates or fibrils so as to promote their clearance by “natural” biological means, such as the immune response. 3. In parallel, Prof. Raviv's group is establishing the assembly conditions for β-A (1-40) to provide a good X-ray solution scattering signal.
GENETIC ENGINEERING APPROACHES FOR PREVENTING BRAIN DAMAGE
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Prof. Hermona Soreq: Department of Biological Chemistry, Alexander Silberman Life Sciences Institute, Hebrew University, Jerusalem
"The BSF grant was of major importance on two levels: (1) It enabled us to create transgenic animal lines long before this service was available at the Hebrew University (HU). (2) It strengthened the HU’s links with Baylor College of Medicine (BCM), in general. Thus, Dr. Efrat Lev-Lehman, a Ph.D. student of mine, and Dr. Ron Broide, who was a Post-Doctoral Fellow in my laboratory, went to BCM to continue their training. At present, I am collaborating with Prof. De Biasi at BCM, as a direct continuation of the joint effort initiated during our last active BSF grant." |
