Revealing protein dynamics in asymmetric cell divisions: key to correct cell function and prevention of developmental disorders

This BBSRC DTP studentship provides an exciting opportunity to join a vibrant scientific community studying cell division using cutting-edge technologies (https://www.ncl.ac.uk/medical-sciences/research/research-themes/chromosome-biology/). 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) and PAR function is known to be disrupted in cancer, neurodevelopmental disorders and cardiopathies to name a few. Here we propose to uncover the biophysical mechanism behind clustering dependent flow-sensing using genetics, novel biomolecular tools, cutting-edge microscopy, and physical modelling.

- Dr Rodriguez leads an active and well-established research group in the asymmetric cell division field. The group (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 2^nd 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 9^th January 2023.