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  Understanding the dynamics and function of protein clustering in cell polarisation


   Faculty of Medical Sciences

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  Dr J Rodriguez, Dr Adam Wollman, Dr H Kusumaatmaja  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

This BBSRC DTP studentship provides an exciting opportunity to join a vibrant scientific community studying cell division using cutting-edge technologies (https://research.ncl.ac.uk/celldivisionbiology/). We are seeking an enthusiastic and highly motivated student keen to investigate the fundamental principles of asymmetric cell division, critical for embryo development and tissue integrity.

Many proteins oligomerise and form clusters at the cell membrane. This property can control the activity (i.e. signalling capacity of receptors) and the dynamics of proteins. We and colleagues have proposed that clustering can direct proteins to different parts of the membrane by tapping into cytoplasmic flows generated by shear forces from the dynamic cytoskeleton (Gascon,2020). These biophysical mechanisms can mediate the local/asymmetric activation of signalling pathways, being critical to cellular function and to the development of organisms. Despite their importance, these phenomena are not well understood. To study these processes we take advantage of the C.elegans one-cell stage embryo where clusters of membrane proteins become asymmetrically localised during cell division, regulating cell fate. These proteins are known as PAR proteins, which are conserved polarity regulators, involved in the functional compartmentalisation of most cells (i.e. neurons, epithelial, and asymmetrically dividing cells). Here we propose to uncover the biophysical mechanism behind clustering dependent flow-sensing using cutting-edge microscopy, image analysis and physical modelling.

- Dr Rodriguez leads an active and well-established research group in the asymmetric cell division field. Dr Rodriguez (https://www.ncl.ac.uk/medical-sciences/people/profile/josanarodriguez.html) is based in the Biosciences Institute at Newcastle University, which is a highly successful research institute (ranked 2nd nationally for research outputs in REF2014) where PhD students contribute to the majority of our papers and members have access to state of the art equipment.

- Dr Wollman is a microscopy expert, leading a research group designing and building new microscopes, imaging assays and software (https://www.ncl.ac.uk/medical-sciences/people/profile/adamwollman.html). The group comes from a diverse background and provides extensive interdisciplinary training.

- Prof. Halim Kusumaatmaja has a strong track record in theoretical soft matter and biophysics. Prof Kusumaatmaja (https://sites.google.com/site/kusumaatmaja/home) is based in the Department of Physics at Durham University, one of the premier physics departments in the UK (ranked joint 1st for research impact in REF2014). Interdisciplinary research between physical and biological sciences is a key priority at Durham University, such as through the establishment of the Durham Biophysical Sciences Institute.

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 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 closing date for applications is 10th January 2022 at 5.00pm (UK time).

Biological Sciences (4) Mathematics (25) Physics (29)

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

Going with the flow: insights from Caenorhabditis elegans zygote polarization. Phil. Trans. R. Soc. B (2020) 375:20190555
Morphogenetic degeneracies in the actomyosin cortex. eLife (2018) 7:e37677
aPKC Cycles between Functionally Distinct PAR Protein Assemblies to Drive Cell Polarity. Dev Cell (2017) 42:400
Staphylococcus aureus toxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration. FASEB (2019) 33(3): 3807-3824
Transcription factor clusters regulate genes in eukaryotic cells. eLife (2017) 6 :e27451
Lattice Boltzmann Method: Principles and Practice. Springer (2017)
Wetting of phase-separated droplets on plant vacuole membranes leads to a competition between tonoplast budding and nanotube formation. PNAS 118, e2024109118 (2021)
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