Fixed-term

FULLY FUNDED PhD – The structural and molecular basis of substrate specificity of the thioesterases APT1 and APT2

Project Description A prominent protein modification found in all eukaryotic species is S-acylation, the attachment of hydrophobic acyl chains onto cysteine side chains. S-Acylation regulates the localisation, stability, interactions, and function of numerous proteins, and thereby affects cellular processes like growth, migration, differentiation, and communication. S-acylation is reversible and is regulated by many zDHHC (on) and APT/ABHD (off) enzymes, however, in contrast to many other enzymes that mediate post-translational regulation of proteins, we currently lack fundamental knowledge about these enzymes and their contribution to cell physiology. This project will provide an important advance in this area by uncovering mechanisms whereby de-S-acylation enzymes recognise their specific substrate partners. The project will provide a broad range of training outcomes including, expertise in cutting-edge molecular and structural analyses, data analysis and team working skills, and networking and presentation skills gained through attendance at relevant conferences. There will also be training in a range of generic areas including research ethics and research integrity, data management, and responsible research. This project will support a large multidisciplinary project with multiple partner labs across the UK, applying multidisciplinary Team Science approach to deliver fundamental new insights into the role of S-acylation in cell physiology. You will join a dynamic and supportive team, working collaboratively across two research groups within the College of Medical, Veterinary and Life Sciences, with access to state-of-the-art facilities and mentorship tailored to your career development. Both groups have a strong track record of interdisciplinary research and publication in high-impact journals. Candidate Profile We are looking for a highly motivated individual with a background in molecular or structural biology, biochemistry, or a related field. Prior experience in protein biochemistry is desirable but not essential. Candidates available to start in October 2026 will be prioritised. Application Details Please submit a CV, cover letter, and contact details for two referees via the application portal. Informal inquiries are welcome and encouraged. Funding Notes UK Student fees covered. Apply Now

Research Assistant-Translational Pharmacology and Immunology Laboratory (TPI)

Job description Job Purpose The Translational Pharmacology and Immunology Laboratory (TPI), headed by Professor Maria Libera Ascierto, is at the heart of translational & experimental cancer research and clinical biomarker discovery at the University of Glasgow (UofG). Based in the School of Cancer Sciences, the TPI is the driver of biomarker development and clinical application, mainly in support of clinical trials enrolling patients visiting the Beatson West of Scotland Cancer Centre. The TPI also acts as a central laboratory for processing, storage and analysis of samples derived from patients enrolled in clinical trials of novel therapies sponsored by pharmaceutical companies. Major professional responsibilities of the post holder are to support translational studies in accordance with Good Clinical Practice (GCP), and led by Prof Maria Libera Ascierto,  that are aimed to process human samples derived from patients, including clinical trial participants, and assess them by using ex-vivo immunological assays (eg Immunogenicity Assays to measure immune cell activation, proliferation, and cytokine production, Drug Toxicity and Efficacy assays and Cell Function Monitoring) and spectral cytometry evaluations to boost in-dept-immune phenotype of peripheral blood and disaggregated tumours, monitor disease progression, treatment response and appropriate treatment dosage of novel clinical trials and immune-oncology (IO) treatments. The main duties & responsibilities of the post-holder are dependent on (1) the specific project or clinical trial and (2) the biomarker strategy and design under the direction of Prof Maria Libera Ascierto. These, in turn, may be in response to the requirements and objectives that emerge from the Glasgow Adult ECMC and CRUK CDD’s investigators. Main Duties and Responsibilities 1. Plan and conduct assigned research activities based on spectral cytometry to assist with research project and business operations requiring biological sample, mainly whole blood, PBMC and digested tumours. 2. Responsible for performing and documenting ex vivo immunological assays (eg Immunogenicity Assays to measure immune cell activation, proliferation, and cytokine production, Drug Toxicity and Efficacy assays and Cell Function Monitoring) in accordance with TPI procedures and regulatory guidelines. 3. Document research outputs including sample information, analysis and interpretation of all data, maintaining records and databases, drafting technical/progress reports and manuscript as appropriate. 4. Support the safe transport, handling, processing, storage and analysis of biological specimens derived from patients enrolled in clinical trials according to Good Clinical Practice (GCP) and under the supervision of TPI Head. Take responsibility for following and maintaining Clinical and Research Governance protocols, monitoring compliance and escalating matters for further management attention as appropriate. 5. Develop, optimize and standardize multicolour (up to 40 colours) – flow cytometry immune panels for clinical trials samples evaluations. 6. Contribute to Corrective and Preventive Action (CAPA) experimental investigations, deviations, and resolutions as appropriate. 7. Responsible for performing and documenting flow cytometry and spectral cytometry analytical procedures in accordance with TPI procedures and regulatory guidelines. 8. Assists in troubleshooting and process improvements to increase data quality, lower costs, or reduce turnaround times to include, updating standard procedures, assisting with troubleshooting. 9. Performs and documents calibration and maintenance of laboratory Flow Cytometry and additional equipment as assigned. 10. Performs and documents hands on training for other lab personnel in areas of proven competency as assigned. 11. Assist the TPI Head in the development of proposals to secure funding from internal and external bodies to support future research based on immune phenotype. 12. Collaborate with colleagues and participate in group meetings/seminars/workshops organized by TPI /School/College/University and wider community, including the ECMC Network. 13. Contribute to the organisation, supervision, mentoring and training of undergraduate and/or postgraduate students and less experienced members of the project team to ensure their effective development in spectral cytometry and flow cytometry. 14. Perform administrative tasks related to the activities of the Flow TPI research group, Budgets/Expenditure. 15. Keep up to date with current knowledge and recent advances in the field/discipline. 16. Engage in continuing professional development activities as guided by the TPI Head. 17.  Perform all of the above-mentioned activities, and undertake any other duties of equivalent standing, in conjunction with and under the guidance of the Translational Pharmacology and Immunology Head, Prof Maria Libera Ascierto. 18. Contribute to the enhancement of the international profile of the TPI in line with the University’s Strategic Plan, World Changers Together Knowledge, Qualifications, Skills and Experience Knowledge/Qualifications Essential: A1 SCQF Level 10 (Honours degree) in Biology, Immunology or equivalent. A2 Records of appropriate GCP and GCLP trainings to ensure public safety. A3 A comprehensive and proven knowledge of biomarker discovery and application using whole blood cells and tumour digests Skills Essential: C1 Proven knowledge of processing and storage of blood and tumour cells samples according to GCP standards and suitable for downstream flow cytometry assessments and ex-vivo immunological assays C2 Research creativity and cross-discipline collaborative ability as appropriate C3 Excellent communication skills (oral and written), including public presentations and ability to communicate complex data/concepts clearly and concisely C4 Excellent interpersonal skills including team working and a collegiate approach C5 Appropriate workload/time/project/budget/people management skills C6 Extensive IT and data analysis/interpretation skills as appropriate C7 Self-motivation, initiative and independent thought/working C8 Problem solving skills including a flexible and pragmatic approach Experience Essential: E1 Proven experience in translational medicine research experience in spectral cytometry performed on human samples E2 Proven experience in translational medicine research experience in spectral cytometry or conventional flow data analysis using R software, and/ or FlowJo E3 Proven experience in GCLP settings or CRO providing Flow cytometry services using high quality standards (eg. Q2 solutions) E4 Proven ability to deliver quality outputs in a timely and efficient manner E5 Proven ability to deliver ex-vivo immunological assays performed on human samples (eg Immunogenicity Assays to measure immune cell activation, proliferation, and cytokine production, Drug Toxicity and Efficacy assays and Cell Function Monitoring) E6 Evidence of an emerging track record of high-quality research publications in spectral cytometry immune- phenotype or a a relevant field(eg conventional Flow Cytometry) ​ Informal enquiries should be directed to Professor Maria Ascierto, Maria.Ascierto@glasgow.ac.uk ​ Terms and Conditions Salary will be Grade 6, £33,951 – £37,694 per annum. This post is full-time (35

Research Associate

Job description Job Purpose To make a leading contribution to discovery and translational research exploring the role of creatine and homoarginine in cardiovascular health and disease. The post is laboratory based and funded by a British Heart Foundation programme grant awarded to Dr Craig Lygate. The post holder will have a PhD in a relevant discipline with extensive hands-on experience of standard biochemistry and molecular biology techniques, e.g. protein quantification, RT-PCR, molecular cloning and cell transfection. They will have the experience and depth of knowledge to develop new assays, troubleshoot when there are problems, and help supervise the work of others in the group. The post holder will contribute to the formulation and submission of research publications and proposals. Main Duties and Responsibilities Perform the following activities in conjunction with and under the guidance of the Principal Investigator: 1.      Plan and conduct research as outlined in the BHF programme grant and according to group and School research strategy. 2.      Document research outputs including analysis and interpretation of data, maintaining records and databases, drafting technical reports and papers as appropriate. 3.      Develop and enhance your research profile and reputation and that of the School and University, including establishing and sustaining a history of independent and joint publications in high quality international peer-reviewed journals. 4.      Presentation of work at international and national conferences, at internal and external seminars, webinars, colloquia, and workshops. 5.      Keep up to date with current knowledge and recent advances in the field (i.e. cardiac energetics, homoarginine metabolism, and myocardial biology). 6.      Take a leading role in the identification of potential funding sources and assist in the development of proposals to secure funding from internal and external bodies to support future research. 7.      Take a leading role in developing and maintaining collaborations with colleagues across the University and academic community. 8.      Take a leading role in team meetings and School research group activities to enhance the wider knowledge, outputs, and culture of the school. 9.      Take a leading role in the organisation, supervision, mentoring and training of undergraduate and postgraduate students and less experienced members of the project team to ensure their effective development. 10.  Perform administrative tasks related to the activities of the research group and School, including grant budgeting and writing/reviewing SOPs, risk assessments and Health & Safety documentation. 11.  Engage in personal, professional and career development, to enhance both specialist and transferable skills in accordance with desired career trajectory. 12.  Undertake any other reasonable duties as required by the Principal Investigator or Head of School. 13.  Contribute to the enhancement of the University’s international profile in line with the University’s Strategic Plan. Knowledge, Qualifications, Skills and Experience Knowledge/Qualifications Essential: A1.  Normally Scottish Credit and Qualification Framework level 12 (PhD) in biochemistry, biomedical sciences, pharmacology or equivalent plus track record of emerging independence within a research/professional environment, or alternatively possess professional qualifications and experience equivalent to PhD level plus the requisite experience A2. Specialist theoretical and practical knowledge of the following: protein biochemistry, cellular and molecular biology Desirable: B1. An up-to-date knowledge of the wider subject area of cardiovascular science B2. A UK Home Office Personal Licence (or equivalent training) Skills Essential: C1. Extensive practical skills in biochemistry and molecular biology techniques (e.g. protein & gene expression analysis, mammalian cell culture, molecular cloning, and the generation of transfected cell lines) C2. Excellent communication skills (oral and written), including public presentations and ability to communicate complex data/concepts clearly and concisely C3. Research creativity with the ability to develop key research collaborations C4. Excellent interpersonal skills including team working and a collegiate approach C5. Excellent organisational and time management skills C6. High level data analysis, statistical, and interpretation skills C7. Excellent problem-solving skills including a flexible and pragmatic approach C8. Clear ability to self-motivate and use initiative, working effectively as an individual C9. Excellent attention to detail and ability to work methodically Desirable: D1. Practical skills in HPLC D2. Practical skills in the study of protein post-translational modifications D3. Analysis of metabolomic and proteomic datasets Experience Essential: E1. Relevant research experience commensurate with an early career researcher E2. A track record of presentation of research results at conferences E3. Experience of scientific writing with a track record of first-author publications in quality journals E4. Contribution to researcher development, for example through the supervision of master’s and PhD students. E5. Contribution to the local research community via activities such as journal club presentation, committee membership etc. Informal Enquiries should be directed to Dr Craig Lygate, Craig.Lygate@glasgow.ac.uk ​ Terms and Conditions Salary will be Grade 7, £41,064 –  £44,746 per annum. Please note due to the available funding for this project we will be able to appoint the successful candidate for only up to SP35  £44,746. This post is full time (35 hours per week) and has funding for up to 10 May 2031 The University of Glasgow has a responsibility to ensure that all employees are eligible to live and work in the UK.  If you require a Skilled Worker visa to work in the UK, you will be required to meet the eligibility requirements of the visa route to be assigned a Certificate of Sponsorship. Please note that this post may be eligible to be sponsored under the Skilled Worker visa route if tradeable points can be used under the Skilled Worker visa rules. For more information please visit: https://www.gov.uk/skilled-worker-visa. As a valued member of our team, you can expect: 1 A warm welcoming and engaging organisational culture, where your talents are developed and nurtured, and success is celebrated and shared. 2 An excellent employment package with generous terms and conditions including 41 days of leave for full time staff, pension – pensions handbook https://www.gla.ac.uk/myglasgow/payandpensions/pensions/, benefits and discount packages. 3 A flexible approach to working. 4 A commitment to support your health and wellbeing, including a free 6-month UofG Sport membership for all new staff joining the University  https://www.gla.ac.uk/myglasgow/staff/healthwellbeing/. We believe that we can only reach our full potential through the talents of all. Equality, diversity and inclusion

Uncovering the role of lipid renovation in bacteria-host interactions

Antimicrobial resistance is one of the most serious threats to humans in the 21st century. Understanding antimicrobial resistance mechanisms is pivotal for combating superbugs. Pathogens use many strategies to combat challenges by antimicrobial compounds to better adapt or survive antibiotic insults. This project aims to determine whether there is an overlooked dimension to antimicrobial resistance mechanisms, namely the remodelling of membrane lipids. Lipid remodelling is a process whereby bacteria selectively modify their membrane lipid composition in response to a particular environmental stimulus. Such remodelling potentially plays a role in dictating the permeability and selectivity of the outer membrane, mediating antimicrobial resistance. From a pathogen’s perspective, the lipid bilayer forms the first line of defence against the invasion of an antibiotic. We hypothesize that changes in membrane composition will result in selective recruitment of outer membrane proteins (such as efflux pumps), thus affecting antibiotic trafficking through the membrane. We recently discovered the central pathway responsible for bacterial lipid remodelling and demonstrated that lipid remodelling is common in diverse bacteria. It is present in many clinically important pathogens such as Burkholderia cenocepacia. This pathway is also essential for intracellular survival and plays a key role in subverting host autophagy and the innate immunity response. Using cutting-edge omics (transcriptomics/proteomics), advanced imaging (confocal) and cellular biology approaches (macrophages, autophagy biomarkers), this project aims to determine the link between lipid remodelling, antimicrobial resistance and intracellular survival using B. cenocepacia as the model organism. To apply, please follow the following link: https://sits.bham.ac.uk/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=FR630G&code2=0005 Funding Notes The project is available through MIBTP funding program. For more details, please visit:  https://warwick.ac.uk/fac/cross_fac/mibtp/phd/supervisors/ychen References Shropshire et al. 2023 bioRxiv 2023.05. 30.542800. Jones et al., 2021 ISME J https://doi.org/10.1038/s41396-021-01008-7. Apply Now

Build or destroy? Investigating how plants connect protein synthesis and degradation to regulate protein quality control

Proteins are essential components of cells, and the proteome must be effectively regulated to maintain cellular integrity. A critical contributory step to proteome function is protein synthesis, where mRNAs are translated into polypeptides by the ribosome. However, problems can arise during this process, leading to the production of “bad” proteins that negatively impact cellular function. Defective mRNAs and proteins must be recognised and destroyed, but, surprisingly, mechanisms controlling co-translational protein quality in plants are still largely unknown. We recently identified a family of E3 ubiquitin ligases in the model plant Arabidopsis that function at the interface of mRNA translation and protein destruction. This project will investigate the hypothesis that these ligases are components of an expanded and plant-specific “toolkit” that provides dynamic and stress-responsive functions in translational quality control. There are several key areas where a PhD candidate would focus their investigations: (1) Defining how these E3 ligases dynamically associate with ribosomes, proteasomes and other cellular machineries to form ‘translasomes’ that act as quality surveillance hubs. (2) Characterising their direct proteolytic and mRNA targets. (3) Characterising how their activity is regulated in response to changing translational demands of the cell under optimal and challenged situations. (4)Determining how they contribute to the control of global and stress-responsive mRNA translation and degradation. The research will be largely molecular based and will also include ‘omics’ approaches. The PhD candidate will therefore gain expertise in a wide range of cutting edge and transferable techniques. How to apply: To apply, please follow this link, make an account, and submit an application via the university online admissions portal. This link is unique to the MIBTP programme; please do not use any other link to apply to this project or your application may be rejected: https://sits.bham.ac.uk/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=FR167D&code2=0005 Funding Notes This project is competition-funded via the MIBTP doctoral training partnership. See project description here: https://warwick.ac.uk/fac/cross_fac/mibtp/phd/supervisors/DGibbs/#protein_synthesis Please contact Professor Daniel Gibbs with a CV and cover letter BEFORE applying to this project. Apply Now

How does the brain make decisions when faced with conflicting options?

Every day, we make choices that involve balancing opportunities with risks—but what’s actually happening in our brains as we make these decisions remains largely unknown. A central mystery in neuroscience is how the brain evaluates conflicting options and prioritizes specific actions. Evidence suggests there are sex differences in decision-making and unique vulnerabilities to neurological disorders across genders. Therefore, understanding how the brain makes decisions across contexts and genders holds important medical, economical, and societal benefits. Studying decision-making in mammals is challenging due to the brain’s complexity, but it is feasible in the fruit fly Drosophila, where single cells and circuits can be easily observed and manipulated. Capitalising on these advantages, we discovered a fascinating brain mechanism that allows flies prioritise behaviours during conflicting situations (Cazale-Debat et.al Nature, 2024 doi: 10.1038/s41586-024-07890-3). When animals, including humans, are deeply focused on something they desire—they may become less aware of potential dangers around them. This phenomenon, often referred to as “love blindness,” is a widespread behavioural tendency where the pursuit of a valued reward, like a mate, can overshadow possible risks. In the animal world, this kind of focus can help increase the chances of finding a mate and reproducing, but it also makes individuals more vulnerable to threats, such as predators. In our study, we explored how the brain balances risk and reward during courtship, focusing on male fruit flies. We discovered a neural mechanism controlled by dopamine, a chemical linked to reward and pleasure, which allows the flies to reduce their sensitivity to danger as they get closer to mating. In the early stages of courtship, visual signals alert the flies to nearby threats, activating certain neurons that cause the flies to stop courting. This response is mediated by serotonin, another brain chemical that temporarily inhibits the courtship drive to ensure survival. However, as the male flies advance in the courtship process, the brain gradually shifts gears. Dopamine levels rise, which reduces the response to threats, allowing the flies to stay focused on courtship instead of fleeing from danger. By tracking brain activity, we observed that the closer the flies get to mating, the higher the dopamine levels rise, eventually blocking the pathway that would normally alert them to visual threats. This allows the flies to “tune out” distractions and prioritise mating. In essence, dopamine acts as a sensory filter, adjusting the flies’ perception of threats based on their proximity to achieving their goal. This filtering system enables the brain to prioritise between competing actions, choosing reproduction over survival when it matters most. This PhD project will take this discovery further, aiming to answer key questions: (i) Does this dopamine-driven filtering mechanism also exist in females, and are there sex-specific differences? (ii) Is this neural mechanism applicable to other high-stakes decisions beyond mating versus predator avoidance? (iii) Is this neural mechanism an evolutionarily conserved strategy? As a PhD student on this project, you’ll work at the cutting edge of neuroscience, using state-of-the-art techniques including advanced genetics, neural circuit tracing/connectomics, multiphoton imaging to capture neural activity in live, synaptic tracing, behaving flies, optogenetics, CRISPR for gene editing, and custom coding for data analysis. You will collaborate with researchers working in Germany, UK and Switzerland. This project offers an unprecedented opportunity to uncover decision-making processes during conflicts at remarkable molecular, cellular, and neural circuit level, revealing fundamental principles of brain function across species and sexes. For more information about the Rezaval lab and research please visit: https://www.rezavallab.org/ Please contact Prof Rezaval directly with a cover letter outlining your interest, your background, and why you wish to join her lab in particular. References Mating proximity blinds threat perception. Nature (2024). https://doi.org/10.1038/s41586-024-07890-3. Laurie Cazalé-Debat*, Lisa Scheunemann*, Megan Day, Tania Fernandez-d.V. Alquicira, Anna Dimtsi, Youchong Zhang, Lauren A Blackburn, Charles Ballardini, Katie Greenin-Whitehead, Eric Reynolds, Andrew C Lin$, David Owald, and Carolina Rezaval. A neuronal mechanism controlling the choice between feeding and sexual behaviors in Drosophila. Cheriyamkunnel SJ*, Rose S*, Jacob PF, Blackburn LA, Glasgow S, Moorse J, Winstanley M, Moynihan PJ, Waddell S, Rezaval C. Curr Biol. 2021 Neuroscience: How the brain prioritizes behaviors. Barajas-Azpeleta, R, Tastekin I and Ribeiro C. Curr Biol. 2021. Bellen, H., Tong, C. & Tsuda, H. 100 years of Drosophila research and its impact on vertebrate neuroscience: a history lesson for the future. Nat Rev Neurosci 11, 514–522 (2010). https://doi.org/10.1038/nrn2839 Apply Now

Understanding plant development and evolution in the context of environmental responses.

The aim of the project is to understand how plants have adapted to respond to environmental challenges throughout evolutionary time by investigating key plant transcriptional regulators. Understanding these fundamental evolutionary processes enables application of this knowledge to mitigating the current global challenges associated with climate change, including food insecurity and ecological degradation. We have recently discovered new roles for various transcriptional regulators in plant responses to light, sulphur deprivation and flooding/hypoxia. The project will take molecular, genetic, cell biological, ‘omics and evo-devo approaches across a range of potential plant systems to further understand the functions and regulatory networks of the key transcriptional regulators. The project will include comparative work using seed plants (e.g. Arabidopsis, tomato, potato, barley) and non-seed plants (Physcomitrium (moss), Marchantia (liverwort)) and can be flexible to fit the research interests and expertise of the applicant. References Phokas A, Meyberg R, Briones-Moreno A, Hernandez-Garcia J, Wadsworth PT, Vesty EF, Blazquez MA, Rensing SA, Coates JC. DELLA proteins regulate spore germination and reproductive development in Physcomitrium patens. New Phytol. 2023 238 p.654-672 doi: 10.1111/nph.18756. Phokas A, Coates JC. (2021) Evolution of DELLA function and signalling in land plants. Evolution and Development 23 p.137-154 doi: 10.1111/ede.12365 Apply Now

Regulation of apoptosis-induced compensatory cell proliferation and its implications for cancer and tissue regeneration

In multi-cellular organisms, coordinated cell death (e.g. apoptosis) and cell replacement is critical for tissue recovery in response to stress or damage. Although there is not much known about this process at the cellular and molecular level, recent studies including ours have discovered that apoptotic cells can actively induce compensatory proliferation of surrounding cells through a non-apoptotic function of caspases, a family of cysteine-proteases that normally execute apoptosis. This research aims to dissect the molecular anatomy of compensatory cell proliferation following activation of apoptosis. By taking advantages of Drosophila as a model organism, we have developed unique assays to systematically identify and characterize regulators of compensatory cell proliferation. Because apoptosis-induced compensatory cell proliferation has been observed in tissue regeneration and tumorigenesis in multiple organisms including mammals, identification of its underlying regulatory mechanisms in Drosophila will significantly impact our understanding of its physiological role in tissue repair as well as its pathological role in multiple human diseases including cancer. State-of-the-art technologies in Cell Biology, Molecular Biology, Advanced Microscopy Imaging and Drosophila Genetics are employed in this research. Please provide a brief summary of your research experience when making inquiries or registering interest via FindAPhD. Alternatively, you can email the project’s lead supervisor directly with a CV outlining your education and relevant practical experience. To find out more about studying for a PhD at the University of Birmingham, including full details of the research undertaken in each school, the funding opportunities for each subject, and guidance on making your application, you can now order your copy of the new Doctoral Research Prospectus, at: https://www.birmingham.ac.uk/study/postgraduate Please find additional funding text below. For further funding details, please see the ‘Funding’ section. The School of Biosciences offers a number of UK Research Council (e.g. BBSRC MIBTP, https://www.birmingham.ac.uk/research/activity/mibtp/index.aspx) PhD studentships each year. Fully funded research council studentships are available to both UK nationals and overseas students. The deadline for applications for research council studentships is typically in early January each year. Each year we also have a number of fully funded Darwin Trust Scholarships. These are provided by the Darwin Trust of Edinburgh and are for non-UK students wishing to undertake a PhD in the general area of Molecular Microbiology. The deadline for this scheme is also typically in early January each year. Funding Notes All applicants should indicate in their applications how they intend to fund their studies. We have a thriving community of international PhD students and encourage applications at any time from students able to find their own funding or who wish to apply for their own funding (e.g. Commonwealth Scholarship, Islamic Development Bank). The postgraduate funding database provides further information on funding opportunities available at: https://www.birmingham.ac.uk/postgraduate/courses/research/bio/biosciences.aspx Applications to our competitive funding are normally closed in early January each year. Applicants with their own funding are welcome to apply at any time but must go through the same selection process. Please contact the project’s lead supervisor for further information. References 1) Farrell L, Puig-Barbe A, Haque MI, Amcheslavsky A, Yu M, Bergmann A and Fan Y. (2022) Actin remodeling mediates ROS production and JNK activation to drive apoptosis-induced proliferation. PLoS Genetics 18(12): e1010533. 2) Fan Y.*, Wang S., Hernandez J., Yenigun V.B., Hertlein G., Fogarty C.E., Lindblad J.L. and Bergmann A.* (2014) A model for identification of genes involved in apoptosis-induced proliferation in Drosophila. PLoS Genetics 10(1): e1004131. (*corresponding authors) 3) Fan, Y., and Bergmann, A. (2008) Distinct mechanisms of apoptosis-induced compensatory proliferation in proliferating and differentiating tissues in the Drosophila eye. Dev Cell 14, 399-410. Apply Now

The impact of somatic and epigenetic DNA variation on tree adaptation and evolution

In virtually all living organisms, mutations of genomic DNA allow the generation of new traits that, if positively selected, drive adaptation to changing environments and contribute to evolution. In most multicellular organisms, these DNA mutations are propagated only if passed to next generations by creating a mutated progeny. In addition, intra-organism DNA changes also occur and are known as somatic mutations. However, in most cases, somatic mutations are not biologically relevant, as they do not proliferate in adult cells. An important exception to this principle occurs in trees: although all tree adult tissues derive from a single egg cell, different tree branches contain cells that separated and proliferated independently for long time, spanning several tens, or even hundreds of years. Therefore, somatic DNA genetic and epigenetic variation can be propagated clonally in the cell lineage of a new branch, affecting vast tree areas and producing visible phenotypes. This phenomenon is well documented in artificially mutagenized herbaceous plants and clonally propagated fruit trees, and was recently observed occurring in natural forest trees. However, its relevance as a natural mechanism of tree evolution remains deeply unknown. To fill this gap, this project will search for genomic variants generated in different braches of forest trees, dating and mapping them onto the tree’s branching architecture. Then, we will characterize the impact of DNA mutations on gene expression, and their relevance on genome adaptation to environmental changes and stress. Moreover, for each analysed tree, we will estimate the DNA mutation rate and we will investigate possible correlation of DNA mutations with past documented environmental changes and stress. The selected student will apply ground-breaking newly established methods for efficient detection of genomic variations, constituted by Single Nucleotide Polymorphisms (SNPs), indels, genome rearrangements and transposable element (TE) mobilizations. Interesting variants identified will be validated with standard molecular biology techniques, and their relation to environmental stresses will be evaluated, including disease pressure, high temperature, drought and increased atmospheric CO2 concentration. With this project, we will be able to estimate tree genome plasticity operating in natural conditions, and predict the impact of a changing climate to genome evolution and adaptation of forest trees. Funding Notes This project is NOT associated with funding from the University of Birmingham. Applicants will need to obtain their own scholarship or other financial support to cover tuition fees and living costs. All interested candidates MUST contact the lead supervisor of this project by email, including a current CV and statement of interest BEFORE submitting a formal application. The supervisor can support the application of suitable candidate to external studentship if necessary. References Schmid-Siegert, E., Sarkar, N., Iseli, C., et al. (2017). Low number of fixed somatic mutations in a long-lived oak tree. Nature Plants 3, 926–929. Hanlon, V.C.T., Otto, S.P., and Aitken, S.N. (2019). Somatic mutations substantially increase the per-generation mutation rate in the conifer Picea sitchensis. Evolution Letters 3, 348–358. Lanfear, R. (2018). Do plants have a segregated germline? PLOS Biology 16, e2005439. Apply Now

The role of Efflux in Antibiotic Resistance of Clinically Relevant Pathogens

Antibiotics underpin all of modern medicine; they are used to treat bacterial infections, and to prevent infections after surgery and in patients with a suppressed immune system such as those undergoing cancer chemotherapy or organ transplantation. However, bacteria are able to employ various mechanisms to resist the action of antibiotics and the number of infections caused by bacteria that are resistant to antibiotics is increasing globally. This means that bacterial infections are becoming harder to treat. In fact, antibiotic resistant infections kill 700,000 people worldwide every year and this number is rising annually. Additionally, there is a lack of new antibiotics being developed to replace those that we can no longer use. Bacteria become resistant to antibiotics in many ways but one important mechanism is via multi-drug efflux pumps (Darby et al., 2023). These are pumps, found in the membranes of bacterial cells, that can pump antibiotics out of bacterial cells. This reduces the amount of drug inside the bacteria allowing them to survive at higher drug concentrations and therefore, conferring antibiotic resistance. These pumps can export many different classes of antibiotic so the bacteria are resistant to many drugs at the same time, known as multi-drug resistant (MDR). The Resistance Nodulation Division (RND) family of efflux pumps confer antibiotic resistance to many human pathogens, including the foodborne pathogen Salmonella. The main research focus of Dr Blair’s lab is understanding the involvement of RND efflux pumps in antimicrobial resistance. In particular, we are interested in how efflux is controlled and how this impacts the amount of antibiotic that accumulates inside bacterial cells. The team is a welcoming, inclusive environment that focuses on student development and learning while working on important and exciting problems connected to AMR. This project will involve mastering the measurement of many of aspects of microbial physiology including antimicrobial susceptibility, plasmid conjugation, efflux rates and intracellular antimicrobial accumulation. This project will involve training in a range of microbiology and molecular biology skills, likely to include flow cytometry, FACS, bacterial culture, genetic engineering, plasmid conjugation and persistence assays, sequencing and analysis. References 1. Darby, E.M., Trampari, E., Siasat, P. et al. Molecular mechanisms of antibiotic resistance revisited. Nat Rev Microbiol 21, 280–295 (2023). DOI:10.1038/s41579-022-00820-y 2. Siasat and Blair, 2024. Microbial Primer: Multidrug efflux pumps. Microbiology. doi:10.1099/mic.0.001370 Apply Now

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