Applications are invited for a 3-year fully funded PhD studentship starting October 2015.

Background:

Lysosomes are low pH multi-functional organelles that function as recycling compartments, in autophagy, for coordinating cellular responses to the environment and in intracellular calcium homeostasis. Lysosomal dysfunction occurs in a large group of inherited disorders known as the lysosomal storage disorders. In many of these disorders early-onset neuropathology occurs and neurons appear particularly susceptible to lysosomal dysfunction. This project will apply bespoke genome editing using the CRISPR/Cas9 technology to generate in vivo reporters and molecular hooks to probe this fundamental question in molecular medicine: why are neurons hypersensitive to lysosomal dysfunction?

Techniques and approaches:

The project will use both Drosophila and zebrafish as model organisms to take advantage of the speed and power of fly genetics and the high resolution in vivo imaging capabilities of zebrafish. The student will use the CRISPR/Cas9 system of genome editing, molecular biology and genetics to generate multiple in vivo tools that can be used to probe lysosomal function. Then, the student will use a combination of cell biology, live in vivo microscopy, biochemistry, pharmacology and electrophysiology to ask how lysosomal dysfunction impacts on neuronal health and function.

Supervisors and environment:

Dr Richard Tuxworth and Professor Ferenc Mueller will jointly supervise this project. The project will be fully integrated between the two labs, which are housed together. The School of Clinical and Experimental Medicine is situated within the Medical School of the University of Birmingham and is a modern, well-equipped and dynamic environment to study biomedical science.

Person Specification

Applicants must have graduated with, or be predicted to obtain, a minimum of an upper second degree (or equivalent) in a related subject. A Masters degree will be advantageous but is not essential. Applicants with Engineering, Physics or similar first degrees will be considered but are required to be studying/have studied in a related biological topic to Masters level. Evidence of laboratory research experience is essential.

How to apply

Preliminary enquiries are welcome and should be directed to Richard Tuxworth (r.i.tuxworth<στο>bham.ac.uk) or Ferenc Mueller (f.mueller<στο>bham.ac.uk). 

Applications should be directed to Viktorija Ziabliceva (v.ziabliceva<στο>bham.ac.uk).

To apply, please send:

• A detailed CV
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities
• Copies of your degree transcripts
• Evidence of your proficiency in the English language, if applicable

References

Roberts JA et al. (2014). Targeted transgene integration overcomes variability of position effects in zebrafish. Development 141, 715-24.

Nepal C et al. (2013). Dynamic regulation of the transcription initiation landscape at single nucleotide resolution during vertebrate embryogenesis. Genome Res. 23, 1938-50.

Tuxworth RI et al. (2011). The Batten disease gene CLN3 is required for the response to oxidative stress. Hum. Mol. Genet. 20, 2037-47.

Irion U et al. (2014). Precise and efficient genome editing in zebrafish using the CRISPR/Cas9 system.Development 141, 4827-30.