Biophysics Group

Bar-Ilan University

The Mina and Everard Goodman faculty of life sciences

Research Interests

The main activities of the research group are concentrated around the problems of self-assembly of macromolecules and the mechanisms of function of macromolecular structures. The overall experimental approach is based on protein engineering and chemistry combined with various spectroscopic methods.  In particular we invest much efforts in development and application of methods based on ultra-fast fluorescence spectroscopy and time resolved FRET measurements. Naturally, the group is interdisciplinary and includes biochemists, chemists and laser spectroscopists.

Few projects currently run by the members of the research group include:

a)   A study the mechanism of protein folding by means of fast kinetics experiments and by monitoring folding transitions under perturbed equilibrium conditions. The long-range goal of this project is to identify few general basic rules underlying the efficient and fast folding of protein molecules. The working hypothesis is that the genetic information code for the process of folding and therefore we are searching for sub-domain transitions and the order of formation of secondary and tertiary elements of the folded structures of protein molecules in order to unravel the plan of the process of self assembly. Methods for determination of fast changing distributions of intramolecular distances were developed.

     It was shown that residual sub-domain structures that can direct the initial phases of folding do exist and appear to be a common phenomenon.

b)  Proteins can be viewed as nano-machines with moving elements, which perform work by cycling in the entropy/enthalpy plane. We develop methods for determination of fast and ultrafast directed and random motions of segments of macromolecular structures, in the context of their biological function in order to study the conformational dynamics of globular proteins and the structural basis for their function. In particular we are studying the dynamics of flexible multidomain protein molecules.  The main model molecule presently used for this study is the E. Coli Adenylate kinase, a multidomain enzyme molecule. 

c)   The onset of quite a few neurodegenerative diseases involves formation of deposits of protein aggregates in the central nervous system. These are normal proteins that function in the healthy body and at some point undergo changes of conformation into the aggregate forming state. Some of these appear to be “natively unfolded”. We apply spectroscopic methods for detection of intramolecular conformational changes in order to study the earliest steps of the changes of conformations in these proteins and the nature of the so-called “natively unfolded” state of proteins.

d)  Peptide models are used to study the structural elements of protein conformations and the characteristics of the unfolded states of proteins molecules.

e)   In order to improve the temporal and spatial resolution of the spectroscopic monitoring of conformational changes and dynamics of macromolecules we are constantly striving to develop new instruments and methods for detection of fast conformational changes and kinetic experiments.