Discovering Chemical Tools to Target Membranes

Lipids are critically important molecules underpinning a diverse range of essential biological functions. Together with proteins, they are major constituents of all cellular membranes. This means that lipids are involved in virtually every cellular and organismal process (e.g., viral infections, membrane and organelle biology, cell-cell interactions, tissue development and proper functioning of the immune system). Lipid dysfunction is associated with numerous diseases, including cardiovascular disease, cancer, diabetes, and many rare diseases. Despite the huge importance of lipids, it is generally not well understood how lipids and proteins interact with each other within membranes. It has been challenging to study lipids because they cannot be imaged and manipulated as easily as proteins. We will address this issue by using a combination of experimental and computational tools that have been developed in the Ulmschneider and Eggert groups to design and characterise a new class of peptides that can distinguish between membranes of different lipid composition. Cells express many thousand distinct lipid species, leading to the hypothesis that one of the reasons for this diversity is that lipids and proteins interact specifically with each other, both directly and within larger groups called domains, and that these interactions determine membrane properties and function. The goal of this PhD project is to investigate this hypothesis using a highly interdisciplinary and innovative approach ranging from chemical biology, biophysics and computer modelling to cell biology.

In Year 1, you will identify lipid species that peptides bind to using lipidomic mass spectrometry, which is well established in the Eggert group. You will then use biophysical and biochemical studies to characterise these interactions. You will also be trained in molecular modelling and simulationguided design of membrane-active peptides, a technique pioneered in the Ulmschneider group . This will allow the generation of interaction models and membrane targeting peptides and proteins that will then be tested experimentally in future years. In Years 2 and 3, you will expand the analysis to proteins that are involved in membrane trafficking, an area of expertise in the Eggert lab. Membrane trafficking is important in the transmission of cargoes and signals within and between cells and is very suitable to this analysis because it involves vesicles and structures of different sizes, which are amenable to biophysical analysis of properties such as membrane curvature. In Year 4, you will finalise your experimental and computational work and will write your thesis. You will be trained in a broad range of emerging techniques including computational modeling, biophysics, mass spectrometry microscopy and cell biology.

Essential criteria:

Prospective candidates should have a 1^st or 2:1 M-level qualification in Chemistry, or a related subject.

Candidates should be able to demonstrate an aptitude for multidisciplinary research, the ability to work collaboratively in a diverse research environment as will a track-record of problem-solving and independence.

Application Process

1.      Send your CV and cover letter to [Email Address Removed]

2. Complete an online application on the King’s College myApplication system (https://apply.kcl.ac.uk/):

a. Register a new account/login

b. Once logged in, select Create a new application

c. Enter ‘Chemistry Research MPhil/PhD (Full-time/Part-time)' under Choose a programme. Please ensure you select the correct mode of study.

3.      CV submission and online application MUST both be completed by the deadline.

All relevant information regarding eligibility, including academic and English language requirements, is available from the online prospectus.

The deadline for applications is 15^th June 2021. References must be submitted by the 21^st June. We aim to hold interviews in late June/early July. If you require support with the application process, please contact the Chemistry Postgraduate Administrator Cairn Macfarland [Email Address Removed]