Area:
Molecular Biology, General Biophysics
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High-probability grants
According to our matching algorithm, Jordanka Zlatanova is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2004 — 2010 |
Zlatanova, Jordanka |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Single Chromatin Fiber Dynamics Studied Via Magnetic Tweezers @ Polytechnic University of New York
Chromatin is nowadays the focus of enormous research effort, since it is clear that chromatin is not only a way to passively pack long DNA molecules within the confines of a cell nucleus, but is an essential participant in the regulation of all nuclear activities that process genetic information: transcription, replication, repair, recombination. Chromatin structure has to change in time and space to allow all these processes to occur in a highly regulatable manner, in response to external and internal stimuli. Most of the changes in chromatin structure have been attributed to dynamic changes in the post-synthetic modifications of both the histones and the DNA. These modifications act in concert with chromatin remodeling factors and with sequence- or structure-specific protein factors, to loosen the compact higher-order chromatin organization and further open nucleosome structure to allow access of the bulky cellular machineries to the underlying genes.
The emergence of single-molecule methods has provided a powerful set of tools to approach chromatin structure and dynamics in an unprecedented way, allowing real-time observations on the behavior of individual chromatin fibers and assessing the variability among individual representatives of a fiber population. This project is based on the use of magnetic tweezers for single-molecule chromatin fibers studies. In this home-made instrumental set-up, a single DNA molecule is attached by its termini to a surface and a magnetic bead, and chromatin is assembled from purified histones and chromatin assembly factors. The manipulation of the magnetic bead with the help of external magnets allows introducing torsional stress in the DNA molecule in a highly controlled way, as well as stretching it with a defined force. The goal is to understand the behavior of the chromatin fiber upon external application of tension and/or torsion, to mimic similar conditions created by physiological processes in vivo. The specific aims include following chromatin fiber assembly/disassembly in real time as a function of the superhelical density and tension in the DNA tether, and measuring nucleosome strength as a function of histone acetylation and DNA methylation. The new knowledge will be crucial to our understanding of chromatin structure and dynamics, and of the role chromatin plays in regulating DNA transactions.
The work on these projects will have a significant educational impact providing training for graduate and undergraduate students at the interface of biology, physics and chemistry. Students from underrepresented minorities will work towards obtaining a doctoral degree. The educational component will also include development of a new Single-Molecule Biology course for graduate students. The multidisciplinary nature of the projects will stimulate the transition to the integrated scientific approach to research and education the Polytechnic University is aiming to achieve. The University has just created the Othmer Institute for Interdisciplinary Studies, with the mission to promote interdisciplinary science and education. This research will serve as a nucleation core towards achieving this goal.
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