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Investigating the connection between cytoskeletal and mitochondrial homeostasis during ageing


   Faculty of Health and Life Science

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  Dr Natalia Sanchez-Soriano, Dr V Korolchuk  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

With increasing age, our neurons are at risk of damage, leading to the deterioration of sensory, motor and cognitive performance. Furthermore, ageing is the highest risk factor of multiple neurodegenerative diseases. Yet, we know too little about the mechanisms that drive processes of ageing and neuronal decay.

The decay of axons and synapses, is a prominent feature in the ageing mammalian brain, usually amounting to ~40% decrease in neuronal fibres towards high age. While this offers a likely explanation for the observed deterioration in neuronal performance (sensory, motor and cognitive), the cause for this decay is largely unknown. Based on our own work and relevant literature, we hypothesise that there is a causative link between microtubule deterioration, altered organelle biology and the decay of axons and synapses occurring during ageing. The aim of this project is to assess the effect of ageing on mitochondria and establish whether and/or how microtubule deterioration provides a possible underlying mechanism and therapeutical avenue. The project will be broken down into three objectives: a) To establish how ageing affects the transport, function and turnover of mitochondria; b) To investigate how changes in microtubule networks impact on mitochondrial biology in health and during ageing; c) To establish whether microtubule-targeting drugs provide a novel path to improve the health of mitochondria.

This studentship represents a unique opportunity to study mitochondrial biology and the cytoskeleton during ageing. For this, you will use in vivo models of ageing capitalising on the brain of the fruit fly Drosophila, which is a highly efficient model for studies of the cell biology of ageing, fundamental aspects of which are well conserved with humans. You will combine these studies with mammalian cell models and human cells from young and old individuals, in order to study the relevance of your findings and to increase the impact of your research. You will learn advanced imaging techniques, molecular biology and biochemistry, genetics, brain dissections and molecular cell biology techniques. Investigating the connection between altered microtubule networks and defective mitochondria is likely to provide new explanations for neuronal decay and dysfunction and pave the way towards potential therapeutic strategies.  You will be part of a multidisciplinary collaboration between 2 experienced groups: Dr Sanchez-Soriano at the Institute of Systems, Molecular & Integrative Biology (ISMIB, University of Liverpool) and Dr. Viktor Korolchuk at the Biosciences Institute (NUBI, Newcastle University).

Supervisors:

Dr.Natalia Sanchez-Soriano ([Email Address Removed])

sanchezlab.wordpress.com/research

https://www.liverpool.ac.uk/systems-molecular-and-integrative-biology/staff/natalia-sanchez-soriano/

Dr. Viktor Korolchuk ([Email Address Removed])

https://www.ncl.ac.uk/medical-sciences/people/profile/viktorkorolchuk.html

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);

·        a covering letter – clearly stating your first choice project, and optionally 2nd ranked project, 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;

·        copies of your relevant undergraduate degree transcripts and certificates;

·        a copy of your IELTS or TOEFL English language certificate (where required);

·        a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.

In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Interested applicants should contact Dr Sanchez-Soriano to discuss the project: [Email Address Removed]

The deadline for all applications is 12noon on Monday 9th January 2023. 


Funding Notes

Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking. 2016, eLife 2016;5:e14694 doi: 10.7554/eLife.14694.
Tau, XMAP215/Msps and Eb1 jointly regulate microtubule polymerisation and bundle formation in axons. 2021, PLOS Genetics, 6;17(7):e1009647. doi: 10.1371/journal.pgen.1009647. PMID: 34228717; PMCID: PMC8284659.
Drosophila primary neuronal cultures as a useful cellular model to study and image axonal transport. 2022, Methods in Molecular Biology. 2022;2431:429-449. doi: 10.1007/978-1-0716-1990-2_23. PMID: 35412291.
Basal Mitophagy is Suppressed in Cellular Senescence and Mediates Senescence Phenotypes.
Sneak Peek Cell Press, preprint, http://dx.doi.org/10.2139/ssrn.4137695.
mTORC1 activity is supported by spatial association with focal adhesions. 2021, J Cell Biol. 2021 May 3;220(5):e202004010. https://doi.org/10.1083/jcb.202004010.
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