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Developing new tools and technologies to study calcium signalling in the brain’s immune system


   School of Natural and Environmental Sciences

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  Dr Katrina Madden, Dr N Helassa, Dr Adam Wollman  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Calcium is a crucial signalling species supporting almost every process in cellular life. In neuroscience, calcium-mediated signalling events are some of the most important in the interplay of healthy, ageing and diseased cells within the brain, controlling the release of other messenger molecules such as acetylcholine and glutamate. Although the link between microglial calcium signalling and neuronal phenotype has been drawn, there is still a lot to learn about the effect of immune cell calcium signalling on neuronal functions such as plasticity, synapse development and viability. 

In this project you will use high content imaging, an extremely powerful tool to generate a lot of data about cell phenotype, to develop a ‘fingerprint’ of a cell’s behaviour in specific conditions. You will focus on investigating how neurons and microglia respond to each other and within themselves in terms of calcium signalling, particularly in response to inflammatory conditions. 

You will be based primarily at Newcastle University, developing skills in microglia and neuron cell culture, and developing automated imaging assays to study bioactive molecules’ effect on calcium signalling with Dr Kate Madden. Through rotations in the groups of your co-supervisor Dr Adam Wollman at Newcastle University, you will learn to code (e.g. matlab and python) and generate your own automated image analysis pipeline to analyse the data from your assays, in addition to learning biophysical skills at the University of Liverpool with Dr Nordine Helassa, which will enable you to study the engagement of bioactive molecules with key calcium-dependent targets (e.g. CaM, CaMKII and ion channels). 

By the end of this project, you will have acquired a broad range of interdisciplinary skills that are highly sought after in the biomedical research industry. You will feel confident generating and analysing large amounts of data and will have made a big contribution to understanding how calcium signalling works in the brain, especially during inflammation. This could one day help us treat inflammatory diseases of the brain such as neurodegenerative disease and improve the lives of millions of people around the world. 

Note: Dr Kate Madden has the facilities to perform both neuroscience cell biology and synthetic organic chemistry, therefore this project can accommodate either a full neuroscience focus or a chemical biology focus. Informal enquiries are welcome from a wide range of backgrounds spanning cellular neuroscience to chemistry.

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.

Informal enquiries may be made to [Email Address Removed]

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


Funding Notes

CASE 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

A Phenotypic Screen Identifies a Compound Series That Induces Differentiation of Acute Myeloid Leukemia Cells In Vitro and Shows Antitumor Effects In Vivo (2021). Journal of Medicinal Chemistry, 64(21):15608-15628.
CPVT-associated calmodulin variants N53I and A102V dysregulate calcium signalling via different mechanisms (2022). Journal of Cell Science, 135(2):jcs258796.
Ultrafast glutamate sensors resolve high-frequency release at Schaffer collateral synapses. (2018). Proceedings of the National Academy of Sciences of the United States of America, 115(21):5594-5599.
Large scale, single-cell FRET-based glucose uptake measurements within heterogeneous populations (2022). iScience, 25(4):104023.
A CLK1-KKT2 Signaling Pathway Regulating Kinetochore Assembly in Trypanosoma brucei (2021). mBio, 12(3):e00687-21.
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