Job ID:
Job date: 2014-12-09
End Date:
Company : University of Bristol Country : Role : Research Scientist
Job date: 2014-12-09
End Date:
Company : University of Bristol Country : Role : Research Scientist
Job Description:
We seek an enthusiastic Postdoctoral Research Assistant to join a project funded by a 4-year Wellcome Trust Investigator Award to Dr. Ariel Blocker entitled “Molecular mechanisms powering a bacterial toxin injection device”.
Type III secretion systems (T3SSs) are essential devices in the virulence of many Gram-negative bacterial pathogens. They translocate bacterial virulence proteins into eukaryotic host cells to manipulate them during infection 1. T3SSs involved in virulence (vT3SSs) are evolutionarily related to bacterial flagella assembly apparatuses (fT3SSs) 2. The central function of T3SSs, the translocation process, is energised solely by the cytoplasmic and inner membrane export apparatus (CIMEA), which mediates the passage of substrates across the bacterial inner membrane. The cytoplasmic export apparatus (CEA) comprises an ATPase complex attached to the inner membrane T3SS base. The inner membrane export apparatus (IMEA) probably forms the export pore inside the T3SS base. Only the IMEA is essential for export, for which it uses energy derived from the proton motive force. Export is also strongly enhanced by the ATPase. To enter the narrow channel traversing these apparatuses, substrates must carry a targeting motif and become unfolded. But, the architecture of the cytoplasmic and inner-membrane export apparatus is not well defined and how energy from ATP hydrolysis and the proton motive force is utilised to drive substrate export remains obscure. To investigate this, we will focus on the IMEA and how it interfaces with the CEA. For this, we will work on the T3SS with the best-understood CEA, the Salmonella fT3SS. As the CIMEA is the most conserved part of T3SSs what we find there is directly relevant to vT3SSs. Specifically, the postdoctoral research assistant will use a combination of genetic and biochemical studies focused around in vitro reconstitution of export into inverted inner membrane vesicles, in order to investigate these aspects of T3SSs.
The results of this work will enhance efforts towards rational design of chemical inhibitors of these secretion systems, which may become important assets in the fight against ever rising antibiotic resistance.
The postdoctoral research assistant will work tightly with a research technician and PhD student tackling other aspects of the project and with another (more structurally/biophysically-oriented) postdoctoral research assistant due to start a year later, and well as with several collaborating teams, internally and internationally. Candidates will be expected to have at least an upper-second (2.1) class degree or equivalent in a relevant discipline (Biochemistry, Molecular Biology or Microbiology) and to be about to or to have recently completed their PhD in similar areas. Candidates who have demonstrably productive prior research experience in functional analysis of protein translocation across membranes will be favoured. The position is full-time, with with funding secured for 4 years in the first instance.
For informal enquiries contact Dr. Ariel Blocker on +441173312063 or by email at ariel.blocker@bristol.ac.uk. Further information available via: http://www.bristol.ac.uk/cellmolmed/research/infect-immune/blocker/ ; http://www.wellcome.ac.uk/Funding/Biomedical-science/Funded-projects/Awards-made/Investigator-awards-recipients/WTVM054834.htm
The University of Bristol is committed to equality and we value the diversity of our staff and students.
To apply, please click on the Apply button to be redirected to our website, enter the vacancy number into the job search and follow the link to the on line application process.
Closing date for applications 11-Jan-2015
Additional Info:
[Click Here to Access the Original Job Post]
We seek an enthusiastic Postdoctoral Research Assistant to join a project funded by a 4-year Wellcome Trust Investigator Award to Dr. Ariel Blocker entitled “Molecular mechanisms powering a bacterial toxin injection device”.
Type III secretion systems (T3SSs) are essential devices in the virulence of many Gram-negative bacterial pathogens. They translocate bacterial virulence proteins into eukaryotic host cells to manipulate them during infection 1. T3SSs involved in virulence (vT3SSs) are evolutionarily related to bacterial flagella assembly apparatuses (fT3SSs) 2. The central function of T3SSs, the translocation process, is energised solely by the cytoplasmic and inner membrane export apparatus (CIMEA), which mediates the passage of substrates across the bacterial inner membrane. The cytoplasmic export apparatus (CEA) comprises an ATPase complex attached to the inner membrane T3SS base. The inner membrane export apparatus (IMEA) probably forms the export pore inside the T3SS base. Only the IMEA is essential for export, for which it uses energy derived from the proton motive force. Export is also strongly enhanced by the ATPase. To enter the narrow channel traversing these apparatuses, substrates must carry a targeting motif and become unfolded. But, the architecture of the cytoplasmic and inner-membrane export apparatus is not well defined and how energy from ATP hydrolysis and the proton motive force is utilised to drive substrate export remains obscure. To investigate this, we will focus on the IMEA and how it interfaces with the CEA. For this, we will work on the T3SS with the best-understood CEA, the Salmonella fT3SS. As the CIMEA is the most conserved part of T3SSs what we find there is directly relevant to vT3SSs. Specifically, the postdoctoral research assistant will use a combination of genetic and biochemical studies focused around in vitro reconstitution of export into inverted inner membrane vesicles, in order to investigate these aspects of T3SSs.
The results of this work will enhance efforts towards rational design of chemical inhibitors of these secretion systems, which may become important assets in the fight against ever rising antibiotic resistance.
The postdoctoral research assistant will work tightly with a research technician and PhD student tackling other aspects of the project and with another (more structurally/biophysically-oriented) postdoctoral research assistant due to start a year later, and well as with several collaborating teams, internally and internationally. Candidates will be expected to have at least an upper-second (2.1) class degree or equivalent in a relevant discipline (Biochemistry, Molecular Biology or Microbiology) and to be about to or to have recently completed their PhD in similar areas. Candidates who have demonstrably productive prior research experience in functional analysis of protein translocation across membranes will be favoured. The position is full-time, with with funding secured for 4 years in the first instance.
For informal enquiries contact Dr. Ariel Blocker on +441173312063 or by email at ariel.blocker@bristol.ac.uk. Further information available via: http://www.bristol.ac.uk/cellmolmed/research/infect-immune/blocker/ ; http://www.wellcome.ac.uk/Funding/Biomedical-science/Funded-projects/Awards-made/Investigator-awards-recipients/WTVM054834.htm
The University of Bristol is committed to equality and we value the diversity of our staff and students.
To apply, please click on the Apply button to be redirected to our website, enter the vacancy number into the job search and follow the link to the on line application process.
Closing date for applications 11-Jan-2015
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Additional Info:
[Click Here to Access the Original Job Post]