Prof. Elisha Haas, of the Mina and Everard Goodman Faculty of Life Sciences, studies the problems of self-assembly of protein structures, the second genetic code, and the dynamics and mechanisms of function proteins and nucleic acids. His lab’s overall experimental approach is based on protein engineering and chemistry combined with various spectroscopic methods.
In particular they are interested in the development and application of methods based on ultra-fast fluorescence spectroscopy and time resolved Fluorescence Resonance Energy Transfer (FRET) measurements. Haas and his team are an interdisciplinary group of biochemists, chemists and laser spectroscopists.
To characterize the physical mechanisms governing biological processes, Haas and his team take a multidisciplinary approach that combines protein engineering, chemistry, ultra-fast fluorescent spectroscopy and time-resolved FRET measurements. Researchers in his lab aim to identify gene-based signals that underlie the efficient folding of protein molecules, and to characterize the relation of proteins’ conformational dynamics to function.
They are also examining the macromolecular basis of pathological conditions, such as the buildup of protein aggregates in the nervous system that are associated with diseases such as Parkinson’s and Alzheimer’s diseases.
A large part of work conducted by Haas and his team is in studying a-synuclein, a protein that collects in specific nerve cells and seems to be involved in the onset of Parkinson’s disease. Focusing on the mechanism by which soluble a-synuclein molecules that exist in any healthy brain are converted into their toxic form, Haas is working to characterize the earliest and most dynamic phase of this transition under various conditions on the structural level.
In the future, work in his lab can lead to new and potentially important targets for drugs designed to combat the protein aggregation associated with neurodegenerative diseases.
One of the main focuses of Haas’ lab is studying the mechanisms of protein folding by using fast kinetics experiments and by monitoring folding transitions under perturbed equilibrium conditions. Their long-range goal is to identify the basic rules underlying the efficient and fast folding of protein molecules. Their working hypothesis is that the genetic information codes for the process of folding and includes instructions for the “construction” process.
Therefore, they are searching for sub-domain transitions and the order of formation of secondary and tertiary elements of the folded structures of protein.
In addition to studying many aspects of the protein-folding problem, Haas and his team explore the dynamic mechanisms of structure and enzyme activity. They focus on the rate of motion of chain elements, the correlation of such motions, the effects of mutations and ligand binding, and the “crowding” effect, which is very strong inside the living cells.
The team also collaborates with a research group in Case University in Cleveland, Ohio, on a study investigating the conformational change of insulin upon binding to its receptor, and on projects examining DNA bending in relation to specific sequences and gene expression.
In order to improve the temporal and spatial resolution of the spectroscopic monitoring of conformational changes and dynamics of macromolecules, Haas and his team are constantly striving to develop new instruments and methods for the detection of fast conformational changes and kinetic experiments. In the past, theydeveloped ultrafast time-resolved FRET methods.
They are now developing new instruments for measurements of “double kinetics” using stopped flow system (ms resolution), laser T-jump system (ns time resolution), and P-jump (ms time resolution), as well as single-molecule fluorescence detection.