Fixed-term

We are seeking talented, motivated students with a passion for research in Acute Respiratory Distress Syndrome to join Dr Rahul Mahida’s team in the Institute of Inflammation and Ageing at the University of Birmingham (https://www.birmingham.ac.uk/staff/profiles/inflammation-ageing/mahida-rahul.aspx). Applicants should have a first or upper second-class degree in a relevant scientific discipline, and who are self-funded or have typically applied for, or secured funding for their studies from their government, employer or associated charitable organisations. THE BIRMINGHAM ACUTE CARE RESEARCH GROUP Dr Mahida is an Associate Professor in the Birmingham Acute Care Research (BACR) group at the University of Birmingham. His translational research focuses on the role of inflammatory pathways, biomarker identification, extracellular vesicles and macrophage dysfunction in the pathogenesis of acute and chronic respiratory diseases. PROJECT SUMMARY: ARDS is a devastating hyper-inflammatory disorder of the lungs which can be precipitated by various insults, the most common being sepsis. Patients with ARDS require prolonged invasive ventilation and have a high mortality (~40%). Of survivors, 10% develop pulmonary fibrosis sequelae. Extracellular vesicles (EVs) have been implicated in the pathogenesis of ARDS, with prior studies indicating they can transfer pro-inflammatory signals (microRNAs, metabolites, proteins) rapidly between organ compartments and contribute to organ failure. This study aims to recruit critically ill sepsis patients with and without ARDS from the ICU, and pulmonary fibrosis patients, collect their blood and urine samples from which EVs will be isolated, and collect physiological/clinical data longitudinally. EVs will then be characterised in terms of size profile, concentration and surface markers indicating cell or origin. EV cargo will be assessed via a multi-omics approach: small RNA transcriptomics, proteomics, lipidomics and metabolomics. These multi-omic data will be analysed and correlated with clinical phenotype and outcome to develop a robust prognostication model and potentially offer insights guiding use of targeted therapies in both ARDS and Pulmonary Fibrosis. The Institute of Inflammation and Ageing is embedded within the University Hospitals Birmingham NHS Trust, which hosts the largest single-site ICU in Europe and one of the largest regional Interstitial Lung Diseases services in the UK. This enables access to large patient cohorts for clinical, translational and data based studies. PhD projects, using these approaches, answering clinically and/or translationally relevant research questions are available to self-funded or scholarship-funded graduates interested in joining BACR. Applicants with research experience and/or Master’s degree should apply directly to the Institute of Inflammation and Ageing for a 3 or 4 year full-time PhD – https://www.birmingham.ac.uk/postgraduate/courses/research/med/inflammation-ageing.aspx. This route requires applicants to submit a drafted research proposal. Applicants will need to submit the following documentation during the application process. • Detailed CV, including your nationality and country of birth; • Covering letter highlighting your research experience/capabilities and why you wish to undertake a PhD in the team; • Names and addresses of two referees; • Copies of your degree certificates with transcripts written in English; • Evidence of your proficiency in the English language, if applicable. • Evidence of scholarship application/funding or independent funding. Funding notes: Applicants are invited from self-funded or scholarship-funded graduates ONLY Applicants will be self-funded or will have typically applied for, or secured funding for their studies from their government, employer or associated charitable organisations. Overseas graduates require IELTs of 6.5 overall. Applying directly to the Institute of Inflammation and Ageing for either a 3 or 4 year full-time PhD – https://www.birmingham.ac.uk/postgraduate/courses/research/med/inflammation-ageing.aspx. Apply Now

Project Details: One of the focuses in our research group is on immune modulation of Natural Killer (NK) cell in various cancers. We have demonstrated that NK cells in patients with B-cell chronic lymphocytic leukaemia (B-CLL) have reduced expression of activating receptors (including NKG2D and DNAM-2) and increased expression of inhibitory receptors (PD-1), which is associated with reduced cytotoxicity (HM Parry et al Oncotarget, 2016, M Farhat et al Leukemia, 2024). In Pancreatic ductal adenocarcinoma (PDAC), our study has revealed the high production of immunoregulatory cytokine IL-10 from NK cells. Importantly, NK cells show dysfunctional phenotype in tumour tissue that was recapitulated in primary NK cells following co-culture with PDAC organoids (F Marcon et al Oncoimmunology, 2020). In Ovarian cancer, our data showed that NK cell also demonstrated an exhausted phenotype in the tumour tissue. Interestingly, high level expression of PVR (DNAM-1 ligand) was identified and it plays an critical role in NK cell mediated lysis of primary tumour cells (R Pounds et al Frontiers in immunology, 2025). In the tumour microenvironment (TME), NK cell can exhibit both antitumor and tumour-promoting functions. NK cells activity can be significantly impaired within the TME. This project aims to study the interaction of NK cells with TME of Ovarian Cancer. This will be studied using tumour cell lines model and organoids from primary tumour samples. We will then seek to build on observations to work towards development of novel therapeutic approaches towards re-engaging NK cell lysis of Ovarian tumour cells. Person Specification We are seeking talented and motivated students who share our passion for controlling cancer. The West Midlands is a diverse community and we seek to reflect this in our research team. Consideration of equality, diversity and inclusion is central in our ambition. Applicants should have a strong background in biomedical research, and ideally a background in immunology or cancer research. They should have a commitment to research in this area and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant subject. A masters degree in a relevant subject area is desirable. How to apply Informal enquiries should be directed to Dr Jianmin Zuo(j.zuo@bham.ac.uk) Applications should be directed to Dr Jianmin Zuo (j.zuo@bham.ac.uk). To apply, please send: •  A detailed CV, including your nationality and country of birth; •  Names and addresses of two referees; •  A covering letter highlighting your research experience/capabilities; •  Copies of your degree certificates with transcripts; •  Evidence of your proficiency in the English language, if applicable. Funding Notes Self-funded students only

Myelodysplastic syndromes (MDS) are a type of blood cancer that predominantly affect older adults, with a median age at diagnosis of 68 to 75 years. MDS originates at the level of haematopoietic stem/progenitor cells (HSPCs) and often progress to acute myeloid leukaemia (AML). There is no cure for MDS. Current therapies fail in 50-60% of patients, but how patients might be stratified to identify those likely to respond from those who fail therapy is not clear. Our group is interested on understanding the molecular mechanisms of disease progression and therapy resistance. Our work and the unique critical tools we have developed, including induced pluripotent stem cells (iPSCs) from patients with MDS, provide the opportunity to address these questions in the stem and progenitor compartment. This project will further investigate the contribution of specific mutations to the disease phenotype how these mutations influence genome instability in HSPCs and define the vulnerabilities this influence brings. Person Specification Applicants should have a strong background in stem cell/molecular biology. They should have a commitment to research in blood disorders and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant subject. How to apply Applications should be directed to p.garcia@bham.ac.uk. To apply, please send: ·        A Detailed CV, including your nationality and country of birth; ·        Names and addresses of two referees; ·        A covering letter highlighting your research experience/capabilities; ·        Copies of your degree transcripts; ·        Evidence of your proficiency in the English language, if applicable. Applicants will be required to attend an interview. This can be conducted face –to –face, by telephone or skype Funding Notes This is for self-funded PhD students. In addition to the appropriate university fee (UK or international postgraduate research rate) the student will be expected to provide a bench fee of £20K approx., due to the high cost of iPSC cultures and differentiation to HSPCs. PhD projects will be of a total of 4 years, with 3.5 years in the lab and 6 months for thesis write-up. Any time in the write-up only mode will only incur a minimal tuition fee. References Lab website: https://www.birmingham.ac.uk/staff/profiles/cancer-genomic/garcia-paloma.aspx Apply Now

Details The ability of skeletal muscles to regenerate in response to injury, exercise, growth or disease depends on a population of adult skeletal muscle stem cells called satellite cells. With aging, the number and regenerative capacity of the stem cells declines; this contributes to the aging process and ultimately to the loss of muscle mass in elderly people. Cell signalling plays a key role in controlling the balance between proliferation, differentiation and self-renewal (ability to maintain a stem cell pool) in skeletal muscle stem cells. Defects that disrupt this balance contribute to disease progression in muscular dystrophies and to aging. In previous work, we have uncovered a critical role for the Sonic Hedgehog signalling pathway in controlling the activity of skeletal muscle stem cells. However, the importance of this cell signalling pathway in aging remains to be established. Likewise, the cellular process(es) implicated in stem cell aging remain to be elucidated. This project consists in uncovering the mechanisms by which Sonic Hedgehog signalling controls skeletal muscle stem cells during muscle regeneration, and how disruption in Sonic Hedgehog signalling impacts muscle aging. The project will provide advanced training in stem cell biology (culture), molecular techniques (qPCR, RNAseq), imaging (confocal microscopy), and genetics (conditional knockout mouse lines). Science Graduate School As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience the breadth of technologies that are used in academia, industry and many related careers. Visit http://www.sheffield.ac.uk/sgs to learn more. Please apply for this project using this link: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying Funding Notes Note that this project is for self-funded students only. Applicants should enquire about registration fees before applying. First class or upper second 2(i) in a relevant subject. To formally apply for a PhD, you must complete the University’s application form using the following link: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information. References Cruz-Migoni SB, Mohd Imran K, Wahid A, Rahman O, Briscoe J, Borycki AG. A switch in cilia-mediated Hedgehog signaling controls muscle stem cell quiescence and cell cycle progression. BioRxiv doi: https://doi.org/10.1101/2019.12.21.884601 Jaafar Marican NH, Cruz-Migoni SB, Borycki AG (2016). Asymmetric Distribution of Primary Cilia Allocates Satellite Cells for Self-Renewal. Stem Cell Reports. 6(6):798-805. Apply Now

Details G protein coupled receptors (GPCRs) remain one of the key therapeutic targets for the treatment of disease, and while much is known about their pharmacology, it is increasingly clear that the signaling mechanisms used by a specific receptor to modulate cell functions is context specific. Adrenal chromaffin cells have a vital role in the body’s response to stress; through the secretion of catecholamines they mediate the ‘fight-or-flight’ response resulting in increased heart rate, blood pressure and metabolic rate. This project aims to elucidate the molecular mechanisms used by GPCRs to modulate catecholamine secretion from chromaffin cells. Using a combination of patch clamp electrophysiology and live cell fluorescent imaging the interactions between heterotrimeric G protein subunits, their effectors and the protein machinery regulating vesicle docking, priming and fusion will be investigated. Please apply for this project using this link: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying References https://www.sheffield.ac.uk/biosciences/people/academic-staff/elizabeth-seward Apply Now

Details GLP-1 Receptor are G protein coupled receptors that naturally respond to glucagon-like peptide-1 (GLP-1), a hormone produced in the gut in response to food intake. The receptor is the target for the type 2 diabetes and weight loss drug semaglutide. Its actions in the pancreas are well studied however, little is known about the molecular mechanisms responsible for its regulation of secretion from neurons. Using a combination of high resolution live cell fluorescent imaging, electrochemistry and patch clamp electrophysiology, we recently discovered that activation of GLP-1Rs promotes the formation of stable fusion pores in adrenal chromaffin cells to facilitate peptide secretion. The aim of this project is to identify the signaling events and molecules controlling exocytosis which are regulated by GLP-1 receptors in neuro-endocrine cells. Investigations into ligand and location bias within this context could aid the development of the next generation of GLP-1 agonists for the treatment of diverse neurological and cardiovascular disorders. Please apply for this project using this link: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying References GONZÁLEZ-SANTANA, A., ESTÉVEZ-HERRERA, J., SEWARD, E. P., BORGES, R. & MACHADO, J. D. 2021. Glucagon-like peptide-1 receptor controls exocytosis in chromaffin cells by increasing full-fusion events. Cell Reports, 36, 109609. https://www.sciencedirect.com/science/article/pii/S2211124721010470?via%3Dihub Seward Lab https://www.sheffield.ac.uk/biosciences/people/academic-staff/elizabeth-seward Apply Now