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  BBSRC NLD Doctoral Training Partnership: How can proteins sense micro-scale membrane topography?


   Faculty of Medical Sciences

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

About the Project

We are seeking a highly motivated student keen to do molecular cell biology research in a hitherto unexplored regulatory mechanism – how proteins (nanoscale) can sense microscale changes in cell membrane topography/shape? [1,2].The control of protein localisation at the cell membrane is key to cell signalling. Therefore, it is essential that we understand how proteins sense membrane topography. Until now studying this phenomenon has proven to be challenging, due to the difficulty to image molecules in the complex dynamic topography of native membranes. We will exploit novel super-resolution imaging in the C.elegans embryo, which presents naturally occurring membrane protrusions or ruffles preserved by an egg shell. Here we have found that clusters of a family of proteins essential to embryonic development and dysregulated in cancers, PAR-proteins, occur[3].Interestingly we have observed that PAR-cluster size exclusion exists in distinct ruffled regions. The PhD student will use our advanced 3D super-resolution microscopy[4,5,VT-i]to map membrane topography and simultaneously track PAR-clusters in order to answer:

Q1. How does cluster size correlate with the degree of membrane curvature?

Q2. Does membrane curvature or shape regulate the movement of PARs at the membrane and into/out from the membrane?

Q3. What factors regulate the dynamics of PAR-clusters at the membrane in response to membrane curvature/shape?

Q4.How can the identified topography sensing regulators (Q3) impact embryonic development? 

To target these questions, you will be working in an interdisciplinary team of biologist and physicist

and learn: 1) advanced 3D super-resolution microscopy and analyses[4,5,VT-i],2) In vivo Single Molecule Counting and Fluorescence recovery after photobleaching (smFRAP) techniques[4,5],3) genome editing (CRISPRCas9) and protein depletion techniques (RNAi)[6] to identify proteins involved in PAR topography-sensing and 4) embryonic functional studies to understand how membrane shape regulates key processes in embryo development. Moreover, your training will be rounded up with an internship in VisiTech International (VT-i), a company dedicated to the development of novel microscopy solutions, with a wide variety of application within the scientific and medical research.

This project will uncover how membrane topography can regulate PAR-cluster localisation and in turn embryo development. Membrane topography regulating cell function by controlling the dynamics and clustering of a wide-range of peripheral membrane proteins is a novel idea, which deviates from current studies focusing on how proteins can sense nanoscale changes in membrane curvature through protein domains[7].Hence, your findings will have a great potential to impact our fundamental understanding of cell function.

[1]Cannon.et.al.2017(doi:10.1016/j.tibs.2017.10.001);[2]Badvaram.et.al.2022(doi:10.48550/arXiv.2210.12204);[3]Rodriguez.et.al.2017(doi:10.1016/j.devcel.2017.07.007);[4]Stracy.et.al.2019(doi:10.1093/nar/gky1143);[5]Wollman.et.al.2020(doi:10.1016/j.ymeth.2019.06.021);

[VT-i](https://visitech.co.uk/) [6]Fievet.et.al.2013(doi: 10.1038/ncb2639);[7]Antonny.2011(doi:10.1146/annurev-biochem-052809-155121)

Meet the team:

https://www.staff.ncl.ac.uk/josana.rodriguez/

https://wollmanlab.co.uk/

https://visitech.co.uk/vt-isim/

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 15th January 2024. 

Part-Time Study Options

All NLD DTP PhDs are available as part time or full time, with part time being a minimum of 50% of full time. Please discuss potential part time arrangements with the primary supervisor before applying to the programme.

Project CASE Status

This project is a CASE project. Your project will be co-supervised by the non-academic partner organisation, and you will spend 3-18 months on a placement with your CASE partner in their workplace. You will experience training, facilities and expertise not available in an academic setting, and will build business and research collaborations. Your CASE partner will also contribute an additional £1,000 per year to your Research and Training Support Grant.

Biological Sciences (4)

Funding Notes

BBSRC NLD DTP programme – starting October 2024.
UKRI provide the following funding for 4 years:
• Stipend (2023/24 UKRI rate £18,622)
• Tuition Fees at UK fee rate (2023/24 rate £4,712)
• Research support and training grant (RTSG).
Note - UKRI funding only covers UK (Home) fees. The DTP partners have various schemes which allow international students to join the DTP but only be required to pay home fees. Home fees are already covered in the UKRI funding, meaning that successful international candidates do not need to find any additional funding for fees.

References


Phil. Trans. R. Soc. B (2020) 375:20190555.
eLife (2018) 7:e37677 and Dev Cell (2017) 42:400.
FASEB (2019) 33(3): 3807-3824.
eLife (2017) 6 :e27451: