PhD opportunities

Information about available funded PhD Positions

Application deadline has passed - EASTBIO (College of Medicine and Veterinary Medicine) Identification of novel metabolic pathways regulating haematopoietic stem cell self-renewal	Dr. Stefano Comazzetto (University of Edinburgh)
Application deadline has passed - EASTBIO (College of Science and Engineering) Chimeric gastruloids for modelling the genetic and metabolic basis for developmental defects	Prof Valerie Wilson (University of Edinburgh)
Application deadline has passed - EASTBIO (College of Science and Engineering) Role Of Mechanosensing In The Development Of Haematopoietic Stem Cells	Prof Alexander Medvinsky (University of Edinburgh)
Application deadline has passed - EASTBIO (College of Science and Engineering) Decoding signalling crosstalks using microfluidics and engineered human pluripotent stem cells	Dr Guillaume Blin (The University of Edinburgh)
Application deadline has passed - EASTBIO (College of Science and Engineering) Can organoids model thymus aging and regeneration?	Prof Clare Blackburn (The University of Edinburgh)
Application deadline has passed - Precision Medicine Project Developing a novel catalytic uncaging drug delivery system to deliver a focal therapy for post-radiotherapy tissue regeneration	Dr Elaine Emmerson (The University of Edinburgh)
Application deadline has passed - Precision Medicine Project Mathematical modeling of pancreatic islet behaviour for the improvement of islet transplants in Type 1 Diabetes	Dr Linus Schumacher (The University of Edinburgh)
Application deadline has passed - Precision Medicine Project Using synthetic biology and quantitative analysis to understand differences in tolerance to tumorogeneic mutations	Prof Sally Lowell (The University of Edinburgh)

EASTBIO (College of Medicine and Veterinary Medicine)

Identification of novel metabolic pathways regulating haematopoietic stem cell self-renewal

Applications accepted up to Friday 17th January 2025

1st Supervisor: Dr. Stefano Comazzetto (University of Edinburgh)

About the Project

A rare population of haematopoietic stem cells (HSCs) sustains life-long blood production. Highly sensitive metabolomic methods have recently discovered a few metabolic pathways controlling HSC maintenance and self-renewal. Notwithstanding these advances, the low numbers of HSCs isolated from tissues precluded the measurement of a significant fraction of the cell metabolome. We thus hypothesize that several other metabolic pathways control HSC self-renewal and function. To assess this previously inaccessible HSC metabolome, we propose to integrate metabolomic and proteomic data from millions of HSCs expanded in culture. To achieve this, my laboratory has established a novel culture system that allows to expand HSCs with physiological levels of metabolites found in their native microenvironment.

In this interdisciplinary project, the student will:1. Characterize the metabolome and proteome of HSCs and progenitors expanded in culture, with expert guidance from Prof. Alex Von Kriegsheim (University of Edinburgh);2. Analyse and combine the information from the generated datasets to identify novel metabolic pathways that potentially regulate HSC self-renewal, with expert guidance from Dr. Antonella Fidanza (University of Edinburgh);3. Test the functional role of identified metabolic pathways on HSC self-renewal using available chemical inhibitors, with expert guidance from Prof. Katrin Ottersbach (University of Edinburgh) and Prof. Vignir Helgason (University of Glasgow).

The student will be part of a highly motivated and vibrant team working on how metabolites regulate normal and malignant haematopoiesis. This highly collaborative project will be primarily carried out at the Centre of Regenerative Medicine at the University of Edinburgh. To deliver this project, the student will receive training in cutting-edge wet lab techniques (HSC culture, flow cytometry analysis and sorting, sample preparation for metabolomics/proteomics, etc.), computational biology analysis (differential expression, enrichment and network analysis, etc.), written and oral communication of scientific findings through regular written reports, presentations at lab and institute level, and attendance to conferences/meetings. The student will gain significant experience in a range of disciplines (stem cell biology, metabolism, computational analysis), data and project management, and working collaboratively.

Understanding how metabolism regulate the self-renewal and function of stem cells is a fundamental question in biology. Our fundamental findings will potentially open to improved culture conditions to expand HSCs in culture for therapeutic applications, and the development of novel therapeutic strategies that promote recovery after bone marrow transplantation. Our results also bear important implications for blood cancers driven by the transformation of normal HSCs, such as chronic myeloid leukaemia.

Funding Notes

UKRI-funded studentships are open to students worldwide and will cover tuition fees at the UK rate, plus a stipend to support living costs and an annual research grant of £5,000 for the first three years of the PhD research. The proportion of international students appointed through the EASTBIO DTP is capped at 30%. All students must meet the eligibility criteria as outlined in the UKRI guidance on UK, EU and international candidates. This guidance should be read in conjunction with the UKRI Training Grant Terms and Conditions, esp. TGC 5.2 & Annex B.

Apply Now

EASTBIO Webpage (to download the documents required for email application process, detailed below)

EASTBIO Application
Equality, Diversity and Inclusion (EDI) survey
Reference Forms can be downloaded via link above

Please send your completed EASTBIO Application Form and EDI survey along with a copy of your academic transcripts to crm-training@ed.ac.uk before the deadline.

You should also ensure that two references have been sent to crm-training@ed.ac.uk by the deadline using the EASTBIO Reference Form.

The EASTBIO team will run a series of 1-hour online sessions in December 2024, open to applicants who have queries about the application process. Please view EASTBIO How to Apply webpage for details.

Unfortunately due to workload constraints, we cannot consider incomplete applications.

EASTBIO (College of Science and Engineering)

Chimeric gastruloids for modelling the genetic and metabolic basis for developmental defects

Applications accepted up to Friday 17th January 2025

1st Supervisor: Prof Valerie Wilson (University of Edinburgh)

2nd Supervisor: Prof Sally Lowell (The University of Edinburgh)

3rd Supervisor: Dr Linus Schumacher (The University of Edinburgh)

About the Project

In this project you will develop cell-based models of mouse and human development and use them to model developmental disorders.

Caudal regression syndrome is a rare developmental disorder whose risk is dramatically increased in diabetic pregnancies where glucose is not well-regulated. An overlapping set of defects are caused by partial loss of function of MNX1 (https://omim.org/entry/176450), a gene that is expressed in neuromesodermal progenitors, which generate the elongating head-to-tail axis (doi: 10.1242/dev.180612; 10.1016/j.devcel.2017.01.015). Therefore this spectrum of defects may be due to malfunction of neuromesodermal progenitors which metabolise glucose differently from their differentiated derivatives (doi: 10.1242/dev.201955). However the molecular, cellular, and metabolic basis for these disorders remains unclear.

In our labs we use pluripotent-cell-based models of embryonic development (mouse and human gastruloids) to understand how neuromesodermal progenitors are normally regulated during development. We have developed quantitative approaches for establishing how cell intrinsic factors and local microenvironment work together to orchestrate differentiation and morphogenesis (https://doi.org/10.1038/s44318-024-00154-w).

In this project, you will generate pluripotent mouse and human cell lines harbouring genetic lesions (e.g. Mnx1) and reporters of metabolic states to investigate these metabolic defects. You will use these cells to generate chimeric gastruloids to understand when, where, and how dysregulation of progenitor cells might result in morphological and differentiation defects, and to unpick the role of glucose metabolism in normal and dysregulated development. You will then use mathematical modelling to examine differences in metabolism between progenitors and their derivatives to generate testable predictions about how metabolic regulation could control morphogenesis.

Funding Notes

Application Portal

Complete our online Application Checklist. From here you can formally apply online. This checklist also provides a link to EASTBIO - how to apply web page. You must follow the Application Checklist and EASTBIO guidance carefully, in particular ensuring you complete all the EASTBIO requirements, and use /upload relevant EASTBIO forms to your online application (as listed below):

EASTBIO Application
Equality, Diversity and Inclusion (EDI) survey
Reference Forms

(downloaded via EASTBIO How to Apply webpage)

You should also ensure that two referees have been contacted in advance of the deadline, and provided with the EASTBIO Reference Form.

Unfortunately due to workload constraints, we cannot consider incomplete applications.

The School of Biological Sciences is committed to Equality & Diversity https://www.ed.ac.uk/biology/equality-and-diversity

EASTBIO (College of Science and Engineering)

Role Of Mechanosensing In The Development Of Haematopoietic Stem Cells

Applications accepted up to Friday 17th January 2025

1st Supervisor: Prof Alexander Medvinsky (University of Edinburgh)

2nd Supervisor: Dr Guillaume Blin (The University of Edinburgh)

About the Project

Haematopoietic stem cells (HSC) emerge from the endothelium of the embryonic dorsal aorta through the process called endothelial-to-haematopoietic transition (EHT). Mechanical cues generated during embryo morphogenesis can be sensed by cells and drive molecular signalling pathways underlying cell fate choice, organ sizes and tumorigenesis. Accumulated evidence suggests that a key transcriptional regulator of mechanosensing called YAP1 is involved in the regulation of EHT. This project is a part of a broader research programme investigating mechanisms of HSC development and involves collaboration with experts in mechanobiology and bioinformatics.

In this project, human pluripotent embryonic stem cells (hPSCs) will be used to study the role of mechanosensing in EHT. Multicolour reporter hPSC lines will be used to monitor EHT dynamics and coordinated YAP1 behaviour in normal and perturbed conditions. Functional screening of genes associated with YAP1 signalling, cell adhesion and cytoskeletal rearrangements will be performed to study their involvement in EHT. Specific aims are:1) Generation of multi-colour reporter hPSC cell lines based on successful YAP1 reporter generated by us. Live imaging and confocal analysis of reporters’ behaviour during EHT. 2) Investigation of interactive links between mechanosensing and EHT using molecular perturbations and microenvironmental cues.3) Computational modelling of EHT integrating mechanosignalling. Techniques: a) Haematopoietic differentiation of hPSCs; b) CRISPR/Cas9 technology and other molecular biology techniques; c) time-lapse/ confocal microscopy; d) multicolour flow cytometry; e) molecular perturbations using knockdown and overexpression techniques; f) microfabrication of adhesion substrates of different geometry and stiffness; g) computational modelling (collaboration with Dr. Adrien Hallou, Oxford). All aforementioned techniques are broadly used in our labs.

References

(1) Medvinsky et al. Embryonic origin of the adult hematopoietic system: advances and questions. Development 2011 Vol. 138 ;1017-31(2) Ivanovs et al., Human haematopoietic stem cell development: from the embryo to the dish. Development 2017 Vol. 144 Issue 13 Pages 2323-2337(3) Crosse et al., Multi-layered Spatial Transcriptomics Identify Secretory Factors Promoting Human Hematopoietic Stem Cell Development. Cell Stem Cell 2020 Vol. 27 Issue 5 Pages 822-839 e8(4) Garcia et al., In vitro modelling of anterior primitive streak patterning with hESC reveals the dynamic of WNT and NODAL signalling required to specify notochord progenitors. Development (in press).(5) Hallou, A. et al., A computational pipeline for spatial mechano-transcriptomics. Nature Methods (in press). (see previous draft: Hallou et al. in BioRxiv). (6) Moya, I. and Halder, G. Hippo-YAP/TAZ signalling in organ regeneration and regenerative medicine. Nat Rev Mol Cell Biol 2019 Vol. 20, 211-226

Funding Notes

Application Portal

EASTBIO Application
Equality, Diversity and Inclusion (EDI) survey
Reference Forms

(downloaded via EASTBIO How to Apply webpage)

You should also ensure that two referees have been contacted in advance of the deadline, and provided with the EASTBIO Reference Form.

Unfortunately due to workload constraints, we cannot consider incomplete applications.

The School of Biological Sciences is committed to Equality & Diversity https://www.ed.ac.uk/biology/equality-and-diversity

EASTBIO (College of Science and Engineering)

Decoding signalling crosstalks using microfluidics and engineered human pluripotent stem cells

Applications accepted up to Friday 17th January 2025

1st Supervisor: Dr Guillaume Blin (The University of Edinburgh)

2nd Supervisor: Dr Lucia Bandiera (The University of Edinburgh)

About the Project

Uncovering the molecular logic allowing cells to integrate multiple signalling cues is of paramount importance to understand how cells commit to distinct functional states during embryonic development, normal tissue function, regeneration and disease.

In the context of human embryonic development, the spatio-temporal dynamics of WNT and NODAL signalling combinatorically dictates the fate of pluripotent cells. We recently evidenced a novel complex interaction between these two ubiquitous pathways across two different time scales (Robles-Garcia et al 2024):

While it was previously known that WNT signalling induces NODAL ligand expression, we uncovered that WNT dosage dictates the downstream temporal dynamics of NODAL production which in turn dictates cell fates.
We showed that WNT signalling induces a rapid and transient activation of SMAD2/3 (the intracellular effector of the NODAL pathway) even before NODAL is expressed, suggesting that WNT can directly activate SMAD2/3 in the absence of NODAL.
Finally, we observed that NODAL inhibition potentiates WNT signalling activity, suggesting that NODAL signalling exerts negative feedback on WNT.

The molecular mechanisms underlying this crosstalk are unknown, and how distinct signalling dynamics define specific transcriptional changes resulting in cell fate decision at the single-cell level remain to be determined.

This PhD project aims to address this important biological question using a multidisciplinary approach:

The supervisory team established a high-throughput automated microfluidic platform featuring 160 chambers that can be seeded with co-cultures of user-defined composition, generates up to 16 time-varying microenvironments, and supports post-experiment retrieval of the cells for downstream analyses (Caringella G. et al, In Press). The project will leverage this powerful system to:

1Characterise the cells response to dynamically changing biochemical stimuli using fluorescence video-microscopy and reporter cell lines enabling real-time monitoring of the WNT-NODAL crosstalk, at the molecular level.
Analyse the downstream transcriptional changes associated with distinct temporal signalling regimes of WNT and NODAL.
Establish novel mechanistic models of the interaction between the two pathways.

Signalling pathways are in principle druggable targets but their complexity and context-dependent kinetics require a systems and control-theoretic approach to elaborate context-aware medical interventions. This project will develop insights and new tools to make a major step towards this goal.

This project is suitable for a candidate with a background in biomedical engineering or in any relevant biological discipline. You will join an enthusiastic and multidisciplinary team to gain training in state-of-the-art techniques in human pluripotent stem cell culture, microfabrication and cell biology.

Funding Notes

Application Portal

EASTBIO Application
Equality, Diversity and Inclusion (EDI) survey
Reference Forms

(downloaded via EASTBIO How to Apply webpage)

You should also ensure that two referees have been contacted in advance of the deadline, and provided with the EASTBIO Reference Form.

Unfortunately due to workload constraints, we cannot consider incomplete applications.

The School of Biological Sciences is committed to Equality & Diversity https://www.ed.ac.uk/biology/equality-and-diversity

EASTBIO (College of Science and Engineering)

Can organoids model thymus aging and regeneration?

Applications accepted up to Friday 17th January 2025

1st Supervisor: Prof Clare Blackburn (The University of Edinburgh)

2nd Supervisor: Dr Elis Chachat (The University of Edinburgh)

3rd Supervisor: Dr Jarrod Dudakov (Fred Hutchison Cancer Centre, Seattle)

About the Project

T cells are essential regulators and effectors of the immune system. Production of a functional, self-tolerant T cell repertoire occurs in a dedicated organ, the thymus, which is exquisitely specialised to mediate this highly complex process. Individuals who lack a thymus also lack T cells and are therefore highly immunocompromised, while defects in normal thymus development cause thymus-dependent primary immunodeficiencies such as the broad spectrum autoimmune disease APECED.

Intriguingly, the thymus is highly active in early life but then undergoes a programmed involution which leads to decreased production of new T cells with age. This is one of the causes of immunosenescence – the age-related decline in immune system function, that at least partly results in the increased susceptibility to new infections and increased cancer incidence that occurs with age. Finding the key to thymic involution could therefore unlock new ways of regenerating the thymus and restoring fully functional immunity.

We have recently developed a miniaturised thymic organoid (mTO) model (Major et al BioRxiv 2024; currently submitted and in revision), in which we can generate multiple in vitro thymi in parallel, each composed of around one thousand cells. Remarkably, mTO mirror the cellular composition and physiological function of the thymus better than any other in vitro model. They are amenable to genetic manipulation and live imaging, making them an exciting new platform for the study of thymus biology as well as for in vitro T cell production.

At present, mTO are established from fetal thymic stromal cells plus the haematopoietic progenitor cells from which T cells are generated. This studentship aims to generate mTO thymus tissue from adult and aged adult mice. Initially, we will use mice as the source of thymus tissue, to allow development of a robust methodology. Once this has been achieved, we will apply the method to human thymus tissue. We will also use the aged thymus-based mTO, in conjunction with bioinformatics analysis of single cell ‘omics data from young and aged thymi, to probe the molecular mechanisms that lead to thymic involution and, by extension, thymus regeneration.

The student will be trained in organoid biology and development of synthetic circuitries using engineering biology approaches, as well as in platform technologies including advanced imaging, flow cytometry, ‘omics analysis and immunology assays. A background in immunology and/or development and stem cell biology is desirable but not essential.

Funding Notes

Application Portal

Complete our online Application Checklist. From here you can formally apply online. This checklist also provides a link to EASTBIO - how to apply web page. You must follow the Application Checklist and EASTBIO guidance carefully, in particular ensuring you complete all the EASTBIO requirements, and use /upload relevant EASTBIO forms to your online application (as listed below):

EASTBIO Application
Equality, Diversity and Inclusion (EDI) survey
Reference Forms

(downloaded via EASTBIO How to Apply webpage)

You should also ensure that two referees have been contacted in advance of the deadline, and provided with the EASTBIO Reference Form.

Unfortunately due to workload constraints, we cannot consider incomplete applications.

The School of Biological Sciences is committed to Equality & Diversity https://www.ed.ac.uk/biology/equality-and-diversity

Precision Medicine Project - Developing a novel catalytic uncaging drug delivery system to deliver a focal therapy for post-radiotherapy tissue regeneration

Applications accepted up to Monday 13th January 2025

Supervisor(s): Dr Elaine Emmerson (The University of Edinburgh) & Prof Asier Unciti-Broceta (The University of Edinburgh)

Background

This project aims to develop a novel way of delivering a pharmacological therapy to radiotherapy-injured salivary glands (SGs) to stimulate their regeneration and repair. Radiotherapy is a life-saving treatment for those with HNC (550,000/year worldwide) and >75% undergo radiotherapy as part of their treatment regime. Although radiotherapy is increasingly effective in treating cancer, it also damages/destroys healthy tissues within the radiation field as a side-effect. In particular, damage to the SGs can lead to significant oral health problems, as well as difficulties in speaking, chewing and swallowing, which severely affect quality-of-life. Specifically, the saliva-producing acinar cells are destroyed, resulting in salivary dysfunction and chronic dry mouth (termed xerostomia). Patients rely solely on short-term palliative treatments which temporarily alleviate the symptoms, but do not replicate the consistency and oral protective features of saliva. To date there is no permanent, long-term cure. Our work has shown that cholinergic drugs can effectively stimulate regeneration; however, there is currently no strategy to restrict this locally to the SGs, and significant dose-limiting toxicities would occur if given systemically.

Aims

This project represents a novel, multi-disciplinary approach, that will build upon the discovery of the Emmerson lab, that SG regeneration can be driven by cholinergic stimulation1, coupled with the powerful new chemistry developed by the Unciti-Broceta lab, which relies on catalytic conversion of an inactive drug (prodrug) to an active drug in-situ2-3.

This approach consists of two components:

1. An inactive derivate of the chosen drug (termed a pro-drug) is designed to be specifically activated by a palladium (Pd)-triggered catalytic reaction, which removes the pro-drug portion, leaving an active drug locally.

2. An inert and implantable polymer-based device, functionalised with Pd, is implanted into the tissue to catalyse drug conversion from pro-drug to active drug.

Cholinergic nerves are necessary for SG maintenance. However, over time following radiotherapy innervation of the SG is disrupted, leading to SG dysfunction1. Restoration of cholinergic signalling, via cholinergic drugs, shows therapeutic promise, but such drugs have significant off-target side-effects. We have previously screened a range of cholinergic compounds for their regenerative potential in mouse SG. The student will extend this analysis and take a precision medicine approach by combining the availability of fresh human SG and our ability to culture organotypic SG slices ex vivo4 to explore the heterogeneic response of human SG to cholinergic stimulation. From this the student would chose a candidate compound, which can be structurally altered to a pro-drug, which will be further tested in mouse. We hypothesise that local activation of a cholinergic pro-drug will enable a focal therapy that stimulates regeneration of radiation-damaged SGs.

The PhD student will address this hypothesis via the following aims:

Aim 1: Exploring the response to cholinergic stimulation in human salivary gland organotypic slices4

Aim 2. Designing and synthesising a cholinergic pro-drug

Aim 3. Testing drug conversion and cell replacement in mouse salivary gland organotypic slices4

Aim 4. In vivo examination of drug conversion to regenerate radiation-induced SG

This would providea way of restoring SG function after cancer treatment whilst limiting systemic side-effects. Such a therapeutic option has never yet been explored for those living with the side-effects of cancer treatment but would help tackle a major clinical problem.

Training Outcomes

The student will be given training in research methods and state-of-the-art techniques, including drug synthesis and mass spectroscopy (by members of the Unciti-Broceta lab), tissue culture, immunofluorescent and transcriptional analysis (by members of the Emmerson research group), multicolour flow cytometry and confocal microscopy (by expert core facilities staff) and in vivo techniques (by dedicated veterinary staff and trainers). The student will also gain experience in scientific writing and communication through: 1) regular report writing, 2) presenting at internal seminars and journal clubs, 3) attending conferences and meetings, and 4) participating in lab and Centre-wide public engagement activities.

The student will attend both University-wide and Institute-specific training courses in generic and transferable skills, and will also be encouraged to attend specific workshops that concentrate on the professional development of postgraduates (via the University’s Institute for Academic Development programme). The student will also be supported to attend scientific meetings and conferences and to participate in career development activities, such as demonstrating/teaching and public engagement.

References

1. Emmerson, et al. Salivary glands regenerate after radiation injury through SOX2-mediated secretory cell replacement. 2018. EMBO Mol Med. PMID: 29335337

2. Adam, et al. A 5-FU Precursor Designed to Evade Anabolic and Catabolic Drug Pathways and Activated by Pd Chemistry In Vitro and In Vivo. 2022. J Med Chem. PMID: 34979089

3. Ortega-Liebana, et al. Truly-Biocompatible Gold Catalysis Enables Vivo-Orthogonal Intra-CNS Release of Anxiolytics. 2021. Angew Chem Int Ed Engl. PMID: 34730266

4. Elder, et al. Interrogating cell-cell interactions in the salivary gland via ex vivo live cell imaging. J Vis Exp. 2023. PMID: 38047566

Apply Now

Click here to Apply Now

The deadline for 25/26 applications is Monday 13th January 2025
Applicants must apply to a specific project. Please ensure you include details of the project on the Recruitment Form below, which you must submit to the research proposal section of your EUCLID application.
Please ensure you upload as many of the requested documents as possible, including a CV, at the time of submitting your EUCLID application.

Precision Medicine Recruitment Form (878.42 KB / DOCX)

Precision Medicine Project - Mathematical modeling of pancreatic islet behaviour for the improvement of islet transplants in Type 1 Diabetes

Applications accepted up to Monday 13th January 2025

Supervisor(s): Dr Linus Schumacher (The University of Edinburgh) & Prof Shareen Forbes (The University of Edinburgh)

Background

This project aims to improve the outcomes of islet transplantation through mathematical modelling and computational data analysis.

Islet transplantation is treatment for a subset of patients with Type 1 diabetes (T1D) that involves transplanting insulin-producing islets isolated from a deceased donor pancreas into the liver of a person with Type 1 diabetes. The goal of this procedure is to restore the body’s ability to produce insulin, potentially reducing or eliminating the need for insulin injections and improving blood glucose control. The transplanted islets settle in the liver and begin producing insulin. The benefits are improved glucose regulation, reduced risk of severe hypoglycaemia and a return in awareness of hypoglycaemia in those that have lost the ability to sense hypoglycaemia. Insulin independence may be achieved but there is a gradual attrition in graft function. The benefits of transplant need to be balanced with the risks of immunosuppression including an increased risk of infections and certain cancers.

In research, glucose-stimulated insulin secretion (GSIS) tests are used to measure islet function. First phase insulin secretion (release of preformed insulin granules) has not been considered as a metric for islet health. We have measured first phase insulin secretion in perifusion experiments with collaborators in Edmonton, Canada, as well as data on the outcome of transplantations. We plan to statistically analyse these data to establish whether measuring first phase insulin secretion can improve transplant outcomes.

There are a multitude of factors that might influence the ability of islets to engraft after transplantation. We plan to explore these factors in a mathematical model that simulates the proccess of how islets move through and settle into the liver from the transplant site (e.g. portal vein). Input parameters will include (but not be restricted to) islet size distribution and number of transplanted islets. 3D images of cleared livers (in collaboration with Novo Nordisk) will be used to determine a simulation gemeotry representative of rodent liver anatomy.

Aims

Quantify islet perifusion data on first phase insulin secretion and mathematically model the relationship to transplant outcomes (C-peptide and glucose measurements at 4 weeks and 1 year) taking into account other factors (eg. donor age, ischaemic time, islet numbers, recipient age, sex, immunosuppression)

Establish a mathematical modelling framework for islet transplants. The mathematical model would be informed by experimental data and make predictions about which factors could improve islet distribution and/or engraftment. The mathematical model will be kept as simple as possible (for computational efficiency and interpretability) and as complex as necessary to achieve biomedically meaningful representation

Compare outputs of the mathematical model against distribution of islets in experimental 3D images from rodent models to constrain model parameters using statistical inference techniques (such as simulator-based Bayesian inference or surrogate-based machine learning methods)

Use the parameterized model to predict islet distribution after transplantation in human livers, taking into account known differences in anatomy from rodent to human (and difference in transplantation parameters, such as number of transplanted islets).

Screen in silico for factors that might improve the distribution and/or number of engrafted islets

Training outcomes

This project is a good springboard for a student to go into interdisciplinary or biomoedical research in academia or industry. The Centre for Regenerative Medicine provides a stimulating research environment and training opportunities for PhD students. The Schumacher group has extensive experience in building mathematical models and computational data analysis.

This project is ambitious and novel, as no-one has published mathematical models of device-less islet transplantation, but also feasible as models can be based on well-established cell and tissue simulation frameworks (such as PhysiCell [4] or Chaste).

References

Benninger, Piston, Trends Endocrinol Metab, 2014. 25(8): p. 399-406.
Vierra, Jacobson, Mol Metab, 2018. 9: p. 84-97.
Vierra, Jacobson, Sci Signal, 2017. 10(497).
Ghaffarizadeh et al., PLoS Comput. Biol. 14(2): e1005991, 2018.

Apply Now

Click here to Apply Now

The deadline for 25/26 applications is Monday 13th January 2025
Applicants must apply to a specific project. Please ensure you include details of the project on the Recruitment Form below, which you must submit to the research proposal section of your EUCLID application.
Please ensure you upload as many of the requested documents as possible, including a CV, at the time of submitting your EUCLID application.

Precision Medicine Recruitment Form (878.42 KB / DOCX)

Precision Medicine Project - Using synthetic biology and quantitative analysis to understand differences in tolerance to tumorogeneic mutations

Applications accepted up to Monday 13th January 2025

Supervisor(s): Prof Sally Lowell (The University of Edinburgh) & Dr Linus Schumacher (The University of Edinburgh)

Background

Healthy tissues often harbour tumorogeneic mutations. It is not entirely clear why such mutations are sometimes tolerated but at other times lead to disease. There is an increasing appreciation of that surrounding healthy cells (the tumourogenic ‘niche’) play a critical role, but it is not clear how these cells sense and response to mutant cells. If we are able to uncover the molecular and cellular basis of this ‘sense and response’ mechanisms, we can then determine how genetic differences between individuals could explain different “niche responses” and therefore different susceptibilities to disease and to therapy.

In this project we combine two novel synthetic biology technologies to address this question. The Lowell lab have developed a novel ‘neighbour labelling’ system that will enable multi-omic analysis and quantitative image analysis in order to characterise the behavoir of cells within the niche surrounding early cancer cells. Our close collaborators in the neighbouring Pollard Lab have expertise in developing highly specific synthetic enhancers that can be used to deliver ‘neighbour labelling” machinery to particular cell states, including pre-neoplastic or more advanced tumorogeneic states.

This approach will generate quantative data including spatial and temporal information about how cells respond to mutations in their neighbours, based on live imaging and on scRNAseq analysis of synthetically-labelled neighbours of mutant cells. The Schumacher lab have expertise in mathematical modelling of cell-cell interactions, including spatial analysis of the cancer niche.

Aims

1) To combine two existing technologies to establish a cancer-niche-labelling system

2) To apply this system to cell-based models of preneoplasia already established in the supervisor lab

3) To extract and model quantitative information about ‘sense and response’ mechanisms

This will pave the way towards understanding when and how healthy cells are able to suppress tumour formation, and how this process differs between individuals.

Training outcomes

Synthetic biology approaches for cell engineering
Cell- based models of early tumorogenesis
Bioinformatic analysis of ‘omics data
Quantitative image analysis of neighbour relationships
Mathematical modelling of quantitative data to establish rules underlying neighbour relationships.

Apply Now

Click here to Apply Now

The deadline for 25/26 applications is Monday 13th January 2025
Applicants must apply to a specific project. Please ensure you include details of the project on the Recruitment Form below, which you must submit to the research proposal section of your EUCLID application.
Please ensure you upload as many of the requested documents as possible, including a CV, at the time of submitting your EUCLID application.

Precision Medicine Recruitment Form (878.42 KB / DOCX)

MSc By Research: Regenerative Medicine and Tissue Repair Programme

Our MSc by Research in Regenerative Medicine and Tissue Repair is a one-year, full-time, on-campus Masters programme structured around two laboratory-based research projects and a research proposal writing component.

The programme is based at the Institute for Regeneration and Repair (IRR), a purpose-built research environment at the heart of Edinburgh BioQuarter, with a track record in training over 180 postgraduate students.

This MSc by Research is designed to prepare you for a research career in academia or industry, whether you have recently completed an undergraduate degree or are a professional who wants to pursue a career in research. You will gain valuable transferable skills that will be beneficial in a wide range of professions.

MSc By Research: Regenerative Medicine and Tissue Repair website

PhD Opportunities

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If you are looking to join CRM as a PhD student, keep an eye on the FindaPhD website, where all studentships will be advertised.

Search for studendships on FindaPhD.com

Postdoctoral Research

To find a postdoc position, refer to the University of Edinburgh job search page, where any postdoc/PDRA posts will be advertised.

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Self Funded Applicants

We encourage inquiries and applications from self-funded basic and clinical scientists and from candidates who intend to apply for external funding all year round.

Instructions on how to apply as a self funded student

Studentships can include:

Stipend for 3 or 4 years
Tuition Fees
Research Training Costs
Conference Travel Allowance

Please contact relevant principal investigators informally to discuss potential projects and visit our funding opportunities page.

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PhD funding and finance

This article was published on 2024-02-26