People

Faculty

Haran Tali E., Associate Professor

Phone:  (972)-4-8293767
Fax:  (972)-4-8225153

Building/Auditory:  333

General description of research interests

General description of research interests

The main interest of the group is biophysical research on defining the rules for sequence-dependent DNA structure, its mechanical properties, and the mechanism by which DNA structure contributes to the recognition of particular base sequences by regulatory proteins. A related question is whether there exist a code for the interaction of sequence-specific DNA binding proteins with DNA, and whether this code is encoded in the DNA double helix, similarly to the other massages encoded in the double helix - the genetic code and the code for packaging within the nucleosome.

            Current research topics are now focused on the interaction of p53 tumor suppressor protein with its target sites. The tumor suppressor p53 is one of the most central hubs in human cells, connected to a complex network in the living cell. p53 is the most frequently altered gene to be discovered to date in human cancers, and the inactivation of p53 function by these mutations is central to the development of human cancers. Moreover, p53 is also involved in physiological processes unrelated to acute or chronic stress, such as in development, fertility, and the regulation of longevity and ageing. The tumor suppressing activities of p53 as well as other physiological roles of p53 are conducted by its ability to bind to specific DNA sequences in the human genome. How p53 decides between its various cellular functions and what determines the strength of binding of p53 to its response elements at various levels of protein is currently unknown. Our main research methods are experimental measurements of global structure and mechanical (flexibility) properties of p53 response elements using cyclization kinetics of DNA minicircles, together with binding studies by EMSA and transactivation assays in yeast and human cells.

 

Current research topics:

 

(1) Biophysical characterization of wild-type p53/DNA interactions and its relationship to structural properties of the DNA target sites.

(2) High-throughput studies on the dependence of p53/DNA interactions on protein level.

(2) Selectivity in p53/DNA interactions and its mechanistic origin.

(3) Experimental and computational high-throughput studies of spacer and flanking sequence effects on p53/DNA binding.

(4) Structural, biophysical and functional studies on mutant p53 and its interaction with DNA.