BBSRC NLD Doctoral Training Partnership: A serine proteinase inhibitor as a gatekeeper to mammalian skeletal development: from gene editing to gene evolution

Lipids are dysregulated in many conditions, in healthy, developmental and pathological states, with an example being viral infection. Often, these affects are limited to specific subsets or even individual single-cells. To understand how perturbations mechanistically-influence lipid biosynthesis, we need to be able to identify not just changes in the lipids themselves, but also the levels of biosynthetic enzymes, requiring multi-omic analysis. To understand effects at single-cell level, we need to develop new methods to enable this analysis.

Methods for high-throughput study of the proteome at single-cell level by mass spectrometry were first reported in preprint form in 2017, and are now beginning to be adopted more widely, including the SCoPE2 approach. While it is possible to perform analysis of different aspects of cell biology (RNA, protein, histone modifications, lipids) from the same population of cells and attempt to integrate the datasets, the most robust results are obtained when we can sample these different analytes from the same single cells.

In your PhD, you will work with Dr Ed Emmott to develop methods to expand single-cell proteomics to encompass further measurements, focusing on lipid analysis in collaboration with Prof. Yuqin Wang aiming to yield an approach for analysing both proteins and lipids in single-cells within the same LC-MS/MS run, and from the same individual cells. Working with Dr Anjali Seth from our CASE partner Cellenion, we will develop dedicated single-cell multiomics workflows employing the cellenONE system as an end-to-end single cell sample preparation platform. You will validate these approaches using viral models for infection, and benchmark these against bulk proteomic/lipidomic measurements.

In this PhD, you will receive training in mass spectrometry for protein and lipid analysis, cell culture and viral infection, and analysis of mass spectrometry data including R/Matlab. You will be based in Dr Ed Emmott’s lab at the Centre for Proteome Research, University of Liverpool, which is well-equipped with cutting-edge mass spectrometry instrumentation, as well as a cellenONE. You will spend time with Prof. Yuqin Wang at the University of Swansea, to learn lipidomics methods. You will also spend time with our CASE partner Cellenion at their Lyon R&D headquarters, for training on the cellenONE platform, and for methods development support and skills transfer.

This PhD would most suit a candidate familiar with mass spectrometry, for example with a biochemistry or analytical chemistry background.

HOW TO APPLY:

Applications should be made by emailing bbsrcdtp@liverpool.ac.uk 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 bbsrcdtp@liverpool.ac.uk. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to e.emmott@liverpool.ac.uk

The deadline for all applications is 12noon on Monday 22nd July 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.