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A multifunctional genetic probe for networking lysosomal Ca biology

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  • Full or part time
    Dr M Stagi
    Prof M Trost
    Prof Antony Galione
    Dr L Swan
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

The lysosome, once thought to be a cellular ‘trash-can’, is now found to be the key to understanding signalling controlling human ageing, neurodegeneration and a wide range of diseases from diabetes to cancer. Developing tools to understand how the lysosome works will be key to future studies in basic science and industry.

We are looking for a motivated and creative student to help build and analyse a new imaging probe which will allow us to examine calcium signalling in functional lysosomes in live-imaging, proteomic and lipidomic modalities to develop a fine-grained understanding of how lysosomes function in both health and disease.

The use of the genetic probe we are developing makes it easy to isolate, image, and manipulate lysosomes in living cells and in cellular extracts using one transfectable tool, offering many avenues of application to basic and industry-focussed cell biology. The project team offers an excellent depth and breadth of experience in cell biology. The student would have the unique opportunity to be exposed to 3 first-rate university environments: UoL, Newcastle and Oxford. This project will provide intensive training in modern techniques (molecular biology, imaging, proteomics, lipid-omics and data analysis) and expose the student to different scientific environments and complex biological problems, with great prospects for significant publications.The project, supervied by Dr Stagi, UoL, an expert in live imaging and neuronal physiology, will include placements in the all the labs involved in the project: proteomics studies performed in Newcastle under the supervision of Prof Trost, and lysosomal physiology of calcium signalling in Oxford under the supervision of Prof Galione, training in lipid extraction and analysis with Dr Swan, providing a prospective student with a wide range of future career options.


HOW TO APPLY

Applications should be made by emailing [Email Address Removed] with a CV (including contact details of at least two academic (or other relevant) referees), and a covering letter – clearly stating your first choice project, and optionally 2nd and 3rd ranked projects, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University. Applications not meeting these criteria will be rejected.
In addition to the CV and covering letter, please email a completed copy of the Additional Details Form (Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to [Email Address Removed].

Funding Notes

This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£15,009 for 2019-20). The PhD will start in October 2020. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. Please note, there are 2 stages to the application process.

References

Mitochondrial respiratory chain deficiency inhibits lysosomal hydrolysis. AUTOPHAGY (2019), 15(9), 1572-1591. doi:10.1080/15548627.2019.1586256

Loss of TMEM106B Ameliorates Lysosomal and Frontotemporal Dementia-Related Phenotypes in Progranulin-Deficient Mice (2017). NEURON, 95(2), 281-+. doi:10.1016/j.neuron.2017.06.026

Lysosome size, motility and stress response regulated by fronto-temporal dementia modifier TMEM106B (2014). MOL. AND CELL. NEUROSCIENCE, 61, 226-240. doi:10.1016/j.mcn.2014.07.006

The activity-dependent bulk endocytosis proteome reveals a key presynaptic role for Rab11, (2018) Proc Natl Acad Sci USA, Oct 23;115(43):E10177-E10186.

UBQLN2 connects the proteasome with the HSP70 system to promote autophagy-independent protein aggregate clearance, Cell (2016), Aug 11; 166(4):935-49

Phosphoproteomic screening identifies Rab GTPases as novel downstream targets of PINK1, EMBO Journal (2015), 34(22):2840-61

Intracellular sphingosine releases calcium from lysosomes (2015). Elife 4. pii: e10616. doi: 0.7554/eLife.10616.

Nicotinic acid adenine dinucleotide phosphate (NAADP) and endolysosomal two-pore channels modulate membrane excitability and stimulus-secretion coupling in mouse pancreatic beta cells (2015). J Biol Chem 290, 21376-21392.

Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation. (2008) SCIENCE, 321(5894), 1350-1353. doi:10.1126/science.1160741

Lowe syndrome-linked endocytic adaptors direct membrane cycling kinetics with OCRL in Dictyostelium discoideum. (2019) Molecular biology of the cell, 30(17), 2268-2282. doi:10.1091/mbc.E18-08-0510



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