Post-doc position

Richard J. Reece Richard.Reece at man.ac.uk
Mon Mar 30 09:50:00 EST 1998


Characterisation of the regulatory components of transcriptional
activators.

Applications are invited for a biochemist/molecular biologist to join a
well-funded team investigating metabolic signalling pathways affecting
RNA polymerase II transcription (see Platt and Reece (1997) BioEssays,
19, 1001-1010.  The post, available for up to three years, is generously
supported by a project grant  awarded to Dr. Richard J. Reece by the
BBSRC.  This project will focus on the regulation of two transcriptional
activator proteins.  Both of these proteins are transcriptionally inert
in vitro, but can be activated by the addition of metabolic
intermediates of the pathways they control. The interactions between the
transcriptional activators and inducer molecules will be mapped at high
resolution to understand the processes involved in controlling gene
expression.  Such analysis will not only yield a detailed understanding
of the processes of transcriptional regulation in two defined,
interesting, and tractable experimental systems, but will also lead to a
better understanding of the general processes of transcriptional
activation and repression themselves.  The successful applicant will
have relevant experience in molecular biology and protein
characterisation, but most of all we are looking for a talented and
motivated individual to join our team.  The starting salary for this
position will be up to GB strl 17,973 depending upon age and
experience.  Applicants should hold, or will soon be acquiring, a PhD in
a biological science.  Previous postdoctoral experience, relevant to
this position, will be an advantage.  Preference will be given to
applicants who have experience in at least one of the following areas;
yeast genetics, molecular biology, or biochemistry.  Informal enquiries
can be addressed to Dr. Richard J. Reece, tel: 0161 275 5317, e-mail:
Richard.Reece at man.ac.uk.

Project details:
Precise control and regulation of transcription is essential for both
the viability and adaptability of a cell.  The ability of cells to
respond to extra-cellular signals, such as hormones, nutrients, etc., in
a rapid and concerted fashion is critically dependent on being able to
activate specific sets of genes.  The budding yeast, Saccharomyces
cerevisiae, contains a family of related proteins that are involved in
the transcriptional control of genes encoding various metabolic
pathways.  Much is known about the DNA-binding properties of these
proteins, but little is understood concerning the ways in which their
transcriptional activity is regulated.  Factors affecting the
transcriptional activity of two members of this protein family, Put3p
and Ppr1p, will be identified and characterized, biochemically and
genetically, to better understand the processes of gene activation and
repression.

The main focus of the work proposed here is to apply the techniques of
biochemistry and genetics to address the question of how inactive
transcriptional activators bound to their target sequences are converted
into transcriptionally active proteins.  This powerful combination of
approaches will yield important information about these proteins
themselves, but will also give a better understanding of the processes
of transcriptional activation and repression themselves.

References:
Wu, Y., Reece, R.J. and Ptashne, M. (1996) Quantitation of putative
activator-target affinities predicts transcriptional activating
potentials. EMBO J. 15, 3951-3963
Walters, K.J., Dayie, K.T., Reece, R.J., Ptashne, M. and Wagner, G.
(1997) Structure and mobility of the PUT3 dimer. Nature Struct. Biol. 4,
744-750
Swaminathan, K., Flynn, P.J., Reece, R.J. and Marmorstein, R. (1997)
Crystal structure of the PUT3-DNA complex reveals a novel mechanism for
DNA recognition by a protein containing a Zn2Cys6 binuclear cluster.
Nature Struct. Biol. 4, 751-759
Reece, R.J. and Platt, A. (1997) Signaling activation and repression of
RNA polymerase II transcription in yeast. BioEssays. 19, 1001-1010.

Richard J. Reece Ph.D.
School of Biological Sciences
The University of Manchester
2.205 Stopford Building
Oxford Road, Manchester M13 9PT
United Kingdom

Tel/FAX:   +44-(0)-161-275-5317
Email: Richard.Reece at man.ac.uk





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