The research project is based on a hypothesis published by the principal investigator in the end of 2001 in Trends in Genetics

OTKA T-37357

The research project is based on a hypothesis published by the principal investigator in the end of 2001 in Trends in Genetics. The hypothesis proposes a novel role for molecular chaperones. Chaperones buffer several mutations in living cells by correcting the folding damage caused by amino acid changes. This maintenance of the cellular phenotype is severly compromised in aged organisms, where damaged proteins become abundant, and efficiently compete with the silent mutations. The following research areas are investigated:

  1. By the over-expression of damaged proteins in cells and in transgenic mice we examine changes in the metastatic potential, and the incidence rate of atherosclerosis, diabetes and cancer.

  2. We elucidate the role of chaperones in cytoplasmic organization.

We examine signaling after the "poisoning" of chaperones by damaged proteins as well as after the selective inhibition of the Hsp90 chaperone at its novel nucleotide binding site discovered in our laboratory and published in the Journal of Biological Chemistry. This novel binding site enabled us to develop novel screening techniques to identify new anticancer drug candidates.

The research program may change our view on the role of the most ancient cellular defense system, the ubiquitous family of molecular chaperones. The outlined experiments may prove the contribution of chaperones to the etiology of polygenic, civilization diseases, such as cancer, diabetes, or atherosclerosis giving a new paradigm of the field. The planned research will result in a significant contribution to our knowledge on the mechanism and function of molecular chaperones, and will lead to the establishment of novel methods in the medical practice. All of the individual program points resulted and will result in high level publications in international scientific journals. The research project is based on a widespread Hungarian and international collaboration, helps to recruit and develop several gifted high school, university, and graduate students, and finally, gives a framework to establish a novel Hungarian research school with long-term benefits. The research project was a subject of a recent article in New Scientist.

Principal Investigator:

Prof. Peter Csermely

Semmelweis Univ. Dept. Med. Chem. (http://www.chaperone.sote.hu)

Biorex R& D Co. (http://www.biorex.hu)

csermely@ puskin.sote.hu