A postdoctoral position is available in the group of Prof. A. P. Davis, on the MRC-funded project:
“Anion Carriers for Channel Replacement Therapy”.
Anion transport across membranes is a key biological process, vital for the health of cells and organisms. Dysfunctional anion transport (usually due to faulty anion channels) is the root cause of several genetic diseases, the most common being cystic fibrosis.1 Molecules, which could promote chloride transport across membranes could serve as treatments for these diseases, and would certainly be useful tools for biomedical research. We have developed a series of highly powerful anion receptors typified by 1 – 3,2 and with collaborators have shown that many can transport chloride anions across bilayer membranes.3 Most recently we have found that some, especially 3, are active in cells, while showing very low toxicities.4 In this new phase of the work we aim to optimise their properties, establish a full understanding of their behaviour, and realise their potential for medical applications. The project will involve close collaboration with the group of Prof. D. N. Sheppard in the School of Physiology and Pharmacology, who will perform biological testing, and also with that of Prof. P. A. Gale, University of Sydney, who will follow a complementary chemistry programme.
As part of the project team in Bristol, we seek a chemist who will assist in the design of new transporters, synthesize both established and new candidates, and undertake a detailed mechanistic investigation of their mode of action. Applicants should possess expertise in organic synthesis and measurement aspects of supramolecular chemistry. Experience in anion recognition and/or working with bilayer membranes (e.g. vesicles) would be an advantage. Part of the work will involve studying the transporters using electrophysiological methods (e.g. electrical current measurements in planar lipid bilayers). It is not expected that most candidates will be experienced in these techniques, but the ability to adapt to them will be important.
- 1. M. Rowe, S. Miller, E. J. Sorscher, New England Journal of Medicine 2005, 352, 1992. D. C. Gadsby, P. Vergani, L. Csanady, Nature 2006, 440, 477. Z. Cai, J.-H. Chen, L. Hughes, H. Li, D. N. Sheppard, Advances in Molecular and Cell Biology 2007, 38, 109.
- 2. For example: Substrate discrimination by cholapod anion receptors: Geometric effects and the “affinity-selectivity principle”. J. P. Clare et al, Am. Chem. Soc. 2005, 127, 10739-10746. Steroid-based anion receptors and transporters. P. R. Brotherhood, A. P. Davis, Chem. Soc. Rev. 2010, 39, 3633-3647. A Flexible Solution to Anion Transport: Powerful Anionophores Based on a Cyclohexane Scaffold. J. A. Cooper, S. T. G. Street, A. P. Davis, Angew. Chem., Int. Ed. 2014, 53, 5609-5613. High-Affinity Anion Binding by Steroidal Squaramide Receptors. S. J. Edwards, H. Valkenier, N. Busschaert, P. A. Gale, A. P. Davis, Angew. Chem., Int. Ed. 2015, 54, 4592-4596.
- Chloride transport across vesicle and cell membranes by steroid-based receptors. A. V. Koulov et al, Angew. Chem., Int. Ed. 2003, 42, 4931-4933. Development of synthetic membrane transporters for anions. A. P. Davis, D. N. Sheppard, B. D. Smith, Chem. Soc. Rev. 2007, 36, 348-357. Making a Match for Valinomycin: Steroidal Scaffolds in the Design of Electroneutral, Electrogenic Anion Carriers. H. Valkenier, A. P. Davis, Acc. Chem. Res. 2013, 46, 2898-2909.
- Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia. H. Li, H. Valkenier, L. W. Judd, P. R. Brotherhood, S. Hussain, J. A. Cooper, O. Jurček, H. A. Sparkes, D. N. Sheppard, A. P. Davis, Nature Chem. 2016, 8, 24-32.
Contract Type: Open ended (funded for three years)
Hours of Work: 35 hours per weeks
Work Pattern: Full time
Salary Range: £33,199 – £37,345
Closing date for applications: 11:59 pm on the 20th December 2018
Further information and online application: http://www.bristol.ac.uk/jobs/find/details.html?nPostingId=28434&nPostingTargetId=102394&id=Q50FK026203F3VBQBV7V77V83&LG=UK&mask=uobext
For further information on the research group see: http://www.bris.ac.uk/chemistry/people/anthony-p-davis/overview.html (official web page) or http://davis.chm.bris.ac.uk/ (group web page)