PhD Scholarships available in Structural Biology
in the School of Biological Sciences at the University of Auckland,
New Zealand
Applications are invited for PhD scholarships in the following areas:
The structure of insecticidal toxins from Yersinia entomophaga.
(Dr. Shaun Lott, Dr Mark Hurst, Biocontrol and Biosecurity, AgResearch)
The insecticidal tc toxins produced by a number of bacteria form large
(~2.5MDa) complexes, where the assembly of up to seven proteins are
required to show full insecticidal activity. The general architecture
of these complexes has previously been established using single-
particle EM analysis, but the structural details of the complexes, and
their mode of action, remain obscure. This project aims to elucidate
the structures and functions of components of the tc toxin complex
from the bacterium Yersinia entomophaga.
Drug targets from M. tuberculosis.
(Dr. Shaun Lott, Professor Ted Baker)
We have recently solved the structure of several enzymes known to be
essential for the bacterium to cause disease, including anthranilate
phosphoribosyl transferase (AnPRT; TrpD), the enzyme which catalyses
the second committed step in tryptophan biosynthesis, isopropylmalate
synthase (IPMS; LeuA), the enzyme which catalyses the first committed
step in leucine biosynthesis, salicylate synthase (MbtI) which
catalyses the production of salicylate, essential for the production
of the siderophore mycobactin, and others. Through a combination of in
silico modelling and in vitro assay, we have identified a set of weak
AnPRT inhibitors, and are embarking on the structure-guided synthesis
of more potent versions. We plan to use a similar approach with the
other enzymes also, with the intention of producing useful anti-
mycobacterial agents for the future.
Host lipid-induced transcriptional regulation in M. tuberculosis.
(Dr. Shaun Lott, Dr Sharon Kendall, Royal Veterinary College, London)
We have recently showed that the essential transcriptional regulator
KstR, which has previously been implicated in pathogenesis, directly
controls the expression of many lipid metabolism genes in M.
tuberculosis. Additionally, a similar transcriptional regulator,
KstR2, has also been identified to control a smaller regulon. KstR and
KstR2 both belong to the TetR family of transcriptional regulators,
and our hypothesis is that the activation of KstR and/or KstR2 is
triggered by lipid ligands derived from the human host, triggering
bacterial adaptation to the intracellular environment. We are aiming
to structurally and functionally characterise these transcription
factors to discover more about their mode of action.
Novel proteins from Orf virus.
(Dr. Chris Squire, Professor Ted Baker, Prof. Andrew Mercer, Virus
Research Unit, Otago University)
Orf virus is an animal virus, and a member of the poxvirus family. Its
genome sequence shows that in addition to the genes required for
replication and assembly, it encodes genes for a large number of novel
proteins that appear to have no counterparts in other organisms. We
believe that many of these proteins are involved in infection, or in
immune avoidance (by mimicking components of the host immune system).
Some of these have potential therapeutic applications. We have carried
out a preliminary bioinformatic survey, and identified a subset of
these proteins that we predict to have important functions, and well
defined structures. The aim is to express and purify the proteins,
test their predicted functions and determine their 3D structures by X-
ray crystallography.
These scholarships are funded by research grants from the NZ
Foundation for Research, Science & Technology, and include University
Fees, working expenses and a stipend of NZ$25,000 p/a. Candidates
should have a First or Upper Second Class Honours or Masters Degree or
equivalent, and have a strong interest in using protein structure to
elucidate biological function.
Applicants should write to Dr Shaun Lott (s.l...@auckland.ac.nz) or
Prof. Ted Baker (ted.ba...@auckland.ac.nz) in the first instance,
enclosing a CV and an academic transcript, citing reference AGNRF1, by
May 15th 2009. Informal inquiries are welcomed at the same addresses.
Auckland was recently ranked joint 4th in the world in the Mercer
Quality of Living Survey:
http://www.mercer.com/qualityofliving#Top_5_ranking_cities_by_region
More information about living & studying in Auckland can be found here:
http://www.aucklandnz.com/
More information about the School of Biological Sciences at The
University of Auckland can be found here:
http://www.sbs.auckland.ac.nz/uoa/science/about/departments/sbs/about-us.cfm
More information about Dr Shaun Lott’s Research Group can be found here:
http://shaunlott.blogspot.com
More information about Professor Ted Baker’s Research Group can be
found here:
http://lsb.sbs.auckland.ac.nz/users/ted/index.html
--
Dr J. Shaun Lott
AgResearch Senior Lecturer in Structural Biology
Laboratory of Structural Biology & Maurice Wilkins Centre
School of Biological Sciences
3a Symonds Street
University of Auckland
Private Bag 92019
Auckland 1142
New Zealand
t : +64 9 3737599 x87074
f : +64 9 3737416
http://shaunlott.blogspot.com
