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Hashim
M. Al-Hashimi
Associate
Professor of Chemistry and Assistant Research
Scientist in Biophysics
Ph.D., Yale University
Structure and dynamics of nucleic acids and ribonucleoproteins
using NMR spectroscopy
Phone:
(734) 615-3361
Email:hashimi@umich.edu
Research
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Our
laboratory applies solution state NMR spectroscopy
to investigate the molecular basis of RNA function
in processes ranging from gene expression (e.g.
transcriptional activation and translation) to
virion functioning (e.g. genome packaging and reverse
transcription). We make extensive use of new NMR
techniques involving measurements of residual dipolar
couplings in determining global aspects of RNA
structure, dynamics and interaction.
Although
much of our understanding about RNA function comes
from analyses of ground-state conformations, structurally
distinct excited states accessible through molecular
dynamics are frequently the ones carrying out catalysis
and undergoing recognition. A central goal of our
laboratory is to develop and apply NMR techniques
for determining high-resolution RNA structures
as a function of time and other reaction coordinates.
Research involves biochemical preparation/purification
of isotopically labeled RNA samples, design of
NMR experiments, and development of theoretical
frameworks for analyzing data. Specific areas of
interests include the Mg2+ induced folding trajectory
of the 56-nucleotide P5abc subdomain of the Tetrahymena
group I ribozyme important for catalysis, and symmetrical
dimerization of homologous genomic RNA strands
important for HIV-1 viral replication. In another
area, and as part of a multi-institutional RNA
structural genomics program, we are developing
approaches for high throughput RNA structure determination.
These advances will enable large-scale systematic
studies of RNA structure-function relationship
in areas ranging from evolution to structure assisted
design of therapeutics. We are principal users
of 600 MHz and 800 MHz spectrometers, soon to be
equipped with cryogenic probes, and have access
to the Michigan Life Sciences Corridor 900 MHz
NMR facility. The lab is well equipped to carry
out biochemical, biophysical and computational
investigations.
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AWARDS
- National Science Foundation Career
Award (2007)
- Ralph E. Power Junior Faculty Enhancement
Award (2004)
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REPRESENTATIVE PUBLICATIONS
- Zhang, Q., Stelzer, A., Fisher. C. K.,
and Al-Hashimi, H. M.*, Visualizing Spatially
Correlated Dynamics that Directs RNA Conformational
Transitions. Nature , 450:1263-7 2007
- Hansen,
A., and Al-Hashimi, H. M.*, RNA Dynamics
by Carbon Relaxation and Domain Elongation. J.
Am. Chem. Soc. 129:16072-82 2007.
- Bailor,
M., Musselman, C., Hansen, A., Patel, D.
J., and Al-Hashimi, H. M.*, Determining the
Orientation and Dynamics of RNA helices by
NMR Residual Dipolar Couplings, Nat.
Protoc. , 2:1536-46 2007
- Sun, X.,
Zhang, Q., and Al-Hashimi, H. M.*,
Resolving Fast and Slow Motions in the Internal
Loop Containing Stem-loop 1 of
HIV-1 that Are Modulated by Mg 2+ Binding:
Role in the Kissing-duplex Structural
Transition , Nucleic
Acid Res ., 35:1698-713
2007
- Zhang, Q., Sun, X., Watt,
E. W., and Al-Hashimi, H. M.*,
Resolving the Motional Modes
that Code for RNA Adaptation, Science ,
311: 653-6 2006
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