Modelling competition inside the cell: understanding how exogeneous and endogenous mRNAs compete for translational resources

These projects are open to students worldwide, but have no funding attached. Therefore, the successful applicant will be expected to fund tuition fees at the relevant level (home or international) and any applicable additional research costs. Please consider this before applying. 

 Cells in any living system depend on the regulated production of proteins using the information encoded in genes at DNA level. How cells regulate the amount of proteins that they produce is crucially important in biotechnology, during production of therapeutic proteins, and in medicine, when infection of a cell by a virus can change the functioning of the host gene expression system.

The main objective of this project is to apply physics to develop a mathematical model that predicts how protein production is regulated within cells, and specifically, how protein production is affected when foreign mRNAs (e.g. viral) are introduced into a cell. This exciting application of physics will for the first time allow understanding of the highly complex processes that underpin cell functioning in health and disease, as well as every biotechnological process.

To make proteins in the cell, foreign mRNAs are translated into proteins using molecular machines called ribosomes. The ribosomes bind to the mRNA and advance through a series of 3-nucleotide (codon) steps, in doing so adding one amino acid at each step, until the mature protein has been assembled. This process can be mathematically described using a well-established model of transport in statistical physics called Totally Asymmetric Exclusion Process (TASEP). In this model, the mRNA is described by a one-dimensional lattice along which particles (ribosomes) can hop stochastically from site to site.

We have now extended the model to consider other translation resources, such as the small diffusing molecules called transfer RNAs that supply the amino acids to the ribosome. Cellular mRNAs compete for the same pool of translational resources with viral or other foreign RNAs such as those introduced in a biotechnology process, where cells are used as factories to produce proteins of interest for pharmaceutical or food industry purposes. In doing so, the balance of translational resource is distorted. Understanding how the balance between demand and supply for translational resources is distorted is critically important not only to understand gene expression regulation, but also for optimisation of heterologous gene expression.

Using physics, and sophisticated mathematical models of gene expression, the PhD student will work in a highly interdisciplinary team led by 2 supervisors (Physics and Molecular Biology), who have a long-established collaborationon this topic. Training in athematical modelling and molecular biology will be provided, relevant for a wide range of research and other career destinations.

Informal enquiries are encouraged. Please contact Professor Romano (m.romano@abdn.ac.uk) for further information.

Essential Background:

Decisions will be based on academic merit. The successful applicant should have, or expect to obtain, a UK Honours Degree at 2.1 (or equivalent) in Physics.

We encourage applications from all backgrounds and communities, and are committed to having a diverse, inclusive team. 

Application Procedure:

Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php.

You should apply for Physics (PhD) to ensure your application is passed to the correct team for processing.

Please clearly note the name of the lead supervisor and project title on the application form. If you do not include these details, it may not be considered for the studentship.

Your application must include: A personal statement, an up-to-date copy of your academic CV, and clear copies of your educational certificates and transcripts.

Please note: you DO NOT need to provide a research proposal with this application.

If you require any additional assistance in submitting your application or have any queries about the application process, please don't hesitate to contact us at pgrs-admissions@abdn.ac.uk