interdisciplinary skills training in data science, bioinformatics, AI tools and human stem cell techniques.

Providing training in inter-disciplinary research skills, gained by a project in Psychiatric Nutrigenomics, in a research area pioneered by a GW4 Development Award “Nutriomics for Brain Health”, crossing mental health genomics and dietary metabolism, bridging a knowledge gap in mechanistic understanding of how gene–diet interactions influence mental health. The student will investigate the molecular mechanism links FADS2 genetic variants and altered polyunsaturated fatty acid (PUFA) metabolism to psychiatric disorders.

FADS2 encodes fatty acid desaturase converts dietary essential lipids into the long-chain polyunsaturated fatty acids (LC-PUFAs), omega6 arachidonic acid (AA) and omega-3 eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA). Critical for brain development as they regulate neurogenesis, synapse formation, neuronal activity and neuroinflammation. Genetic variation in FADS2 associated with bipolar disorder, while Mendelian randomisation studies support a protective role of omega-3 fatty acids for affective disorders. Parallel in silico studies integrating genetic and neuroimaging data (genome imaging) have shown psychiatric disease risk associated with altered white matter microstructure and disrupted lipid metabolism in astrocytes implicated in its development. Astrocytes are the principal regulators of brain lipid metabolism, providing metabolic, inflammatory and trophic support for neuronal maturation and function. Astrocyte biology offers a good starting position to probe the mechanistic interaction of FADS2 mutation and diet.

Taking an interdisciplinary approach combining wet and dry lab techniques to establish how FADS2 mutation affects astrocyte neurodevelopment and function to elevate psychiatric risk.

Objective 1: FADS2-mediated astrocyte neurodevelopment deficits. Human induced pluripotent stem cells (hiPSC) develop neurons and glial cells from the same neural progenitor cell (NPC) population. Previously we reported high omega 6:3 PUFA ratios affect gene expression during early stages of neurodevelopment. This includes FOXG1, a risk gene associated with neurodevelopmental disorders [1]. Pilot studies further show there is mis-regulation expression of FOXG1, cyclooxygenase (COX)-dependent lipid signalling and calcium regulation genes in FADS2 mutants. Finally, our single-cell RNA-sequencing (scRNAseq) dataset from NPCs has shown both FADS2 and FOXG1 genes are co-expressed in an NPC population fated to become glial cells. We propose FADS2 plays a key role in the neurogenesis of astrocyte cell fate specification. The student will undertake further in silico analysis of our scRNAseq data by co-clustering relevant astrocyterelated genes with FADS2 and FOXG1 positive cell clusters; creating a specific FADS2 associated-wikipathway and deploying the AI-tool scGTP [2] to predict how gene transcription is altered by FADS2 mutation. Student-driven analysis will define a gene set, which they will validate by qRT-PCR of NPC-derived RNA. Training and support will be provided by an experienced team within the GW4 Cardiff, Exeter and the international partner, Maastricht.

Objective 2: Dysfunction of astrocyte-mediated inflammatory response of FADS2 mutant-derived astrocytes. Using our established protocols in human iPSC culture, differentiation and molecular techniques, the student will generate and characterise astrocytes developed in vitro from control and FADS2 null-mutant iPSC. We predict loss of FADS gene will disrupt inflammatory responses in mature astrocytes. The student will design and undertake experiments to invest how FADS2 deficiency alters the inflammatory response, via changes of lipid metabolism and COX signalling. Objective supported by Cardiff.

Objective 3: Signalling between neurons and FADS2-mutant astrocytes. We have previously demonstrated interaction between human oligodendrocytes and neuronal function, and we will now take a similar approach for astrocytes [3]. We propose altered lipid metabolism will modify the astrocyte secretome and its influence on neuronal function. The student will devise a “mix and match” approach to treat control or FADS2 mutant neurons with cell conditioned media from control or mutant astrocytes. They will deploy two functional assays in Cardiff, (MultiElectrode Arrays (MEAs) and calcium flux measurements (FLIPR), to probe neuronal-astrocyte signalling.

Objective 4. Genome and transcriptome imaging to map in vitro experimental findings onto the human brain. The student’s gene sets will be used to computationally model the effects of FADS2 genetic changes on the excitatory-inhibitory balance of the human brain. Proposing molecular cell interactions established in vitro will correlate with brain regions know to be disrupted in psychiatric patients. Using scRNAseq and pathway analysis to seek overlap with psychiatric GWAS data, mapping in silico to brain regions showing altered white matter and used to inform an existing virtual human brain twin (a computational model) and validated against existing functional brain imaging data. With interdisciplinary experience, creating a mechanistic framework, linking PUFA metabolism, astrocyte development and function to psychiatric disease.

A full description of the project can be found on the GW4 BioMed website.

Academic criteria: Applicants for a studentship must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK.

English requirements: IELTS with an overall score of 6.5 with 5.5 in all subskills, or acceptable alternative. Please see our English Language Requirements guidance for more details.

How to Apply

A list of all the projects and how to apply is available on the GW4 BioMed website. You may select up to 2 projects and submit one application per candidate only.

Please complete an application to the GW4 BioMed3 for an ‘offer of funding’. If successful, you will also need to make an application for an 'offer to study' to your chosen institution later.

Please note that we may close the application process before the stated deadline if an unprecedented number of applications are received– check the GW4 BioMed website for details and updates.

If you are shortlisted for interview, you will be notified from Tuesday, 22nd December 2026. Interviews will be held virtually on 26th and 27th January 2027. Studentships will start on 1st October 2027.

Funding Notes

These studentships are funded through GW4 BioMed3 MRC Doctoral Landscape Programme and consist of UK tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£21, 805 p.a. for 2026/27, updated each year).

Additional research training and support funding of up to £5,000 per annum is also available.

GW4 BioMed3 studentships are available to UK and International applicants

References

1.doi.org/10.3389/fcell.2023.1166808;
2. doi.org/10.1038/s41592-024-02201-0;
3. doi.org/10.1016/j.stemcr.2018.11.019

interdisciplinary skills training in data science, bioinformatics, AI tools and human stem cell techniques.

Providing training in inter-disciplinary research skills, gained by a project in Psychiatric Nutrigenomics, in a research area pioneered by a GW4 Development Award “Nutriomics for Brain Health”, crossing mental health genomics and dietary metabolism, bridging a knowledge gap in mechanistic understanding of how gene–diet interactions influence mental health. The student will investigate the molecular mechanism links FADS2 genetic variants and altered polyunsaturated fatty acid (PUFA) metabolism to psychiatric disorders.

FADS2 encodes fatty acid desaturase converts dietary essential lipids into the long-chain polyunsaturated fatty acids (LC-PUFAs), omega6 arachidonic acid (AA) and omega-3 eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA). Critical for brain development as they regulate neurogenesis, synapse formation, neuronal activity and neuroinflammation. Genetic variation in FADS2 associated with bipolar disorder, while Mendelian randomisation studies support a protective role of omega-3 fatty acids for affective disorders. Parallel in silico studies integrating genetic and neuroimaging data (genome imaging) have shown psychiatric disease risk associated with altered white matter microstructure and disrupted lipid metabolism in astrocytes implicated in its development. Astrocytes are the principal regulators of brain lipid metabolism, providing metabolic, inflammatory and trophic support for neuronal maturation and function. Astrocyte biology offers a good starting position to probe the mechanistic interaction of FADS2 mutation and diet.

Taking an interdisciplinary approach combining wet and dry lab techniques to establish how FADS2 mutation affects astrocyte neurodevelopment and function to elevate psychiatric risk.

Objective 1: FADS2-mediated astrocyte neurodevelopment deficits. Human induced pluripotent stem cells (hiPSC) develop neurons and glial cells from the same neural progenitor cell (NPC) population. Previously we reported high omega 6:3 PUFA ratios affect gene expression during early stages of neurodevelopment. This includes FOXG1, a risk gene associated with neurodevelopmental disorders [1]. Pilot studies further show there is mis-regulation expression of FOXG1, cyclooxygenase (COX)-dependent lipid signalling and calcium regulation genes in FADS2 mutants. Finally, our single-cell RNA-sequencing (scRNAseq) dataset from NPCs has shown both FADS2 and FOXG1 genes are co-expressed in an NPC population fated to become glial cells. We propose FADS2 plays a key role in the neurogenesis of astrocyte cell fate specification. The student will undertake further in silico analysis of our scRNAseq data by co-clustering relevant astrocyterelated genes with FADS2 and FOXG1 positive cell clusters; creating a specific FADS2 associated-wikipathway and deploying the AI-tool scGTP [2] to predict how gene transcription is altered by FADS2 mutation. Student-driven analysis will define a gene set, which they will validate by qRT-PCR of NPC-derived RNA. Training and support will be provided by an experienced team within the GW4 Cardiff, Exeter and the international partner, Maastricht.

Objective 2: Dysfunction of astrocyte-mediated inflammatory response of FADS2 mutant-derived astrocytes. Using our established protocols in human iPSC culture, differentiation and molecular techniques, the student will generate and characterise astrocytes developed in vitro from control and FADS2 null-mutant iPSC. We predict loss of FADS gene will disrupt inflammatory responses in mature astrocytes. The student will design and undertake experiments to invest how FADS2 deficiency alters the inflammatory response, via changes of lipid metabolism and COX signalling. Objective supported by Cardiff.

Objective 3: Signalling between neurons and FADS2-mutant astrocytes. We have previously demonstrated interaction between human oligodendrocytes and neuronal function, and we will now take a similar approach for astrocytes [3]. We propose altered lipid metabolism will modify the astrocyte secretome and its influence on neuronal function. The student will devise a “mix and match” approach to treat control or FADS2 mutant neurons with cell conditioned media from control or mutant astrocytes. They will deploy two functional assays in Cardiff, (MultiElectrode Arrays (MEAs) and calcium flux measurements (FLIPR), to probe neuronal-astrocyte signalling.

Objective 4. Genome and transcriptome imaging to map in vitro experimental findings onto the human brain. The student’s gene sets will be used to computationally model the effects of FADS2 genetic changes on the excitatory-inhibitory balance of the human brain. Proposing molecular cell interactions established in vitro will correlate with brain regions know to be disrupted in psychiatric patients. Using scRNAseq and pathway analysis to seek overlap with psychiatric GWAS data, mapping in silico to brain regions showing altered white matter and used to inform an existing virtual human brain twin (a computational model) and validated against existing functional brain imaging data. With interdisciplinary experience, creating a mechanistic framework, linking PUFA metabolism, astrocyte development and function to psychiatric disease.

A full description of the project can be found on the GW4 BioMed website.

Academic criteria: Applicants for a studentship must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK.

English requirements: IELTS with an overall score of 6.5 with 5.5 in all subskills, or acceptable alternative. Please see our English Language Requirements guidance for more details.

How to Apply

A list of all the projects and how to apply is available on the GW4 BioMed website. You may select up to 2 projects and submit one application per candidate only.

Please complete an application to the GW4 BioMed3 for an ‘offer of funding’. If successful, you will also need to make an application for an 'offer to study' to your chosen institution later.

Please note that we may close the application process before the stated deadline if an unprecedented number of applications are received– check the GW4 BioMed website for details and updates.

If you are shortlisted for interview, you will be notified from Tuesday, 22nd December 2026. Interviews will be held virtually on 26th and 27th January 2027. Studentships will start on 1st October 2027.

Funding Notes

These studentships are funded through GW4 BioMed3 MRC Doctoral Landscape Programme and consist of UK tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£21, 805 p.a. for 2026/27, updated each year).

Additional research training and support funding of up to £5,000 per annum is also available.

GW4 BioMed3 studentships are available to UK and International applicants

References

1.doi.org/10.3389/fcell.2023.1166808;
2. doi.org/10.1038/s41592-024-02201-0;
3. doi.org/10.1016/j.stemcr.2018.11.019