3-year PhD studentship in Translational Omics Research at the UCL Great Ormond Street Institute of Child Health Full-time

3-Year PhD Studentship in Translational Omics Research at the UCL Great Ormond Street Institute of Child Health

A three-year PhD studentship funded by Cure DHDDS is available from 1 October 2026, in the Translational Omics Research Group at the UCL Great Ormond Street Institute of Child Health.

This project will be under the supervision of Professor Kevin Mills, Dr Jenny Hällqvist, Dr Wendy Heywood and Professor Philippa Mills.

This project will define how impaired dolichol biosynthesis disrupts glycosylation, protein handling and cellular quality control in DHDDS deficiency. By measuring these processes dynamically with stable isotope tracers and mass spectrometry, the study aims to convert a poorly understood rare disease into a measurable pathway for biomarker discovery, functional diagnostics and therapeutic target identification.

The student will use cutting edge stable isotope tracing, proteomics, lipidomics and state of the art mass spectrometry to build a dynamic cellular model of DHDDS deficiency. This model will track dolichol metabolism, lipid flux, glycoprotein synthesis, protein folding and cellular quality control in real time. During a PhD we aim to create a platform for disease mechanism discovery, new biomarker development, functional diagnostics and future therapeutic testing. The student will work at the interface of rare disease biology, neuronal cell models, iPSC derived organoids, translational omics and therapeutic discovery.

The project will be based in a highly active translational omics laboratory of around 25 researchers with expertise in mass spectrometry, proteomics, metabolomics, lipidomics, rare disease diagnostics and biomarker translation. The group has helped deliver major translational programmes including mass spectrometry testing during the COVID 19 pandemic and the development of the first blood test for Parkinson's disease.

About the Role

Background

DHDDS deficiency is a rare and devastating congenital disorder of glycosylation. It affects dolichol biosynthesis, a core biochemical pathway required for normal protein glycosylation. Despite this, patients often do not show the classical transferrin isoelectric focusing pattern that usually reveals defective glycoprotein synthesis in CDG.

This creates a major biological and clinical puzzle. The disease is clearly driven by a defect in glycosylation biology yet the standard diagnostic readout can appear relatively normal. This suggests that DHDDS deficiency may cause a more subtle, neuronal specific and dynamic failure of glycosylation, protein folding, trafficking and degradation. These hidden defects may be largely invisible in plasma but highly damaging in neuronal cells.

This PhD will tackle that problem directly. By combining stable isotope tracers with high resolution omics and advanced cellular models, the student will measure the movement of metabolites, lipids and proteins through the pathway rather than relying only on static measurements. This will allow the disease process to be watched as it happens.

Hypothesis and Aims

We hypothesise that DHDDS deficiency causes a dynamic failure of dolichol driven glycosylation and protein quality control that is not fully captured by conventional CDG testing. The project will test whether impaired dolichol metabolism disrupts glycoprotein synthesis, protein folding, trafficking and degradation in neuronal and hepatic cell systems. The student will use stable isotope tracers to quantify pathway flux in real time and define the biochemical signature of DHDDS deficiency.

The aims are to build a functional cellular model of DHDDS deficiency, identify disease relevant biomarkers, define the hidden mechanisms linking DHDDS dysfunction to neuronal injury and create a platform for testing candidate therapeutic strategies.

Research Outputs

The project will deliver a stable isotope based cellular model of DHDDS deficiency that can measure dolichol flux, glycoprotein synthesis, protein folding, trafficking and degradation in real time.

It will generate new mechanistic insight into why DHDDS patients lack the classical CDG isoelectric focusing pattern and will identify biochemical markers that better reflect disease activity. The work will also create a platform for testing candidate therapies in neuronal, hepatic and iPSC derived organoid systems.

Expected outputs include targeted mass spectrometry assays, lipidomic and proteomic datasets, mechanistic pathway models, PhD publications, conference presentations and a translational workflow that could be developed into a future functional diagnostic test.

Policy Outputs The policy output is a new model for how ultra rare genetic diseases should be moved beyond diagnosis by sequencing alone. This work could support a shift toward functional biochemical testing in CDG, helping clinicians measure disease activity, monitor treatment response and design biomarker driven trials. In the longer term it could inform NHS rare disease pathways, trial readiness frameworks and orphan therapy development by showing how a hidden cellular defect can be converted into a measurable diagnostic and therapeutic readout.

About You

Applicants should have a keen research interest in metabolism and neurodegeneration but especially in the omic techniques of proteomics and lipidomics. Applicants should have a minimum of an upper second-class UK Bachelor's degree and/or a Master's degree (preferably with a merit or distinction) in a biological sciences preferably biochemistry.

What We Offer

This studentship provides a starting stipend of £23,805 per annum and covers the cost of Home and Overseas tuition fees. The studentship does not cover the costs of the Student Visa application and Immigration Health Surcharge.

Funding is not provided for paid parental and medical leave. Unpaid interruptions can be requested and may be supported.

How to Apply

Enquiries regarding the post can be made to Professor Kevin Mills (kevin.mills@ucl.ac.uk)

To apply, please send a current CV including the contact details of two professional referees as well as a 1-sided A4 cover letter to Professor Kevin Mills (kevin.mills@ucl.ac.uk)

Closing date for applications: 28 July 2026.

Interview date: 10 August 2026

Applications that are submitted without following the correct application process will not be considered. The successful applicant will then be required to apply to and register on the Child Health research degree to take up the studentship.

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