Biomedical Vacation Scholarships - Summer 2024 (Wellcome Trust)

Scientific areas: 

• fundamental processes that underpin biology, to understand more about how life works
• complexities of human health and disease, including clinical and population-based approaches
• development of methodologies, conceptual frameworks, technologies, tools or techniques that could benefit health-related research

Background:

Stem cells play a fundamental role in maintaining intestinal tissue homeostasis and repair in adults. The intestine is a highly regenerative tissue with tissue-specific stem cells located at the bottom of the crypts of Lieberkühn, where the Wnt pathway is a key regulator of stem cell self-renewal, driving intestinal homeostasis and repair. However, in patients with IBD, chronic inflammation disrupts the stem cell population, impairing tissue repair and compromising the intestinal barrier function. Despite extensive research, the exact mechanisms underlying this impairment remain unknown.

To address these knowledge gaps we are utilising self-organising 3D patient-derived organoids as a powerful tool to mimic IBD and study the underlying mechanisms (funded by a Medical Research Council UK grant (780,000 GBP, 3 years), Crohn’s and Colitis pediatric charity UK (50,000 GBP, 1 year), GUTS UK (15,000 GBP, 1 year) and Royal Society UK (20,000 GBP, 1 year). We have been awarded a funding which grants us exclusive access to a omics data from a  large patient cohort in IBD Plexus. Access to the IBD Plexus research-ready molecular data, particularly cohorts with longitudinal studies, would complement our data and greatly enhance our research outcomes. The large sample size and comprehensive molecular data from IBD Plexus would enable us to employ a bioinformatics approach to identify key molecular triggers at different stages of IBD. This will allow us to establish in vitro patient derived organoids (PDO) models that mimic IBD and elucidate the role of stem cells in regenerating the damaged epithelium after chronic inflammation.

The results of our research may have potential clinical applications in precision medicine for IBD management, such as drug testing and screening.

These are the specific aims of the project:

1. To identify gene signatures contributing to molecular pathways triggered by the stem cell niche during chronic inflammation conditions.
2. To establish 3D patient-derived organoid cultures that are exposed to inflammatory conditions mimicking IBD

We hypothesise that a bioinformatics approach can be employed to identify underlying signalling pathways that govern stem cell regeneration process that are altered in IBD in order to develop, characterise, and validate a 3D intestinal organoid platform as relevant models that can be used for therapeutic development.

The main research question of this project is can we develop an appropriate patient derived organoid model that can effectively recapitulate the disease severity so that personalised medicine can be used to improve the quality of life for those suffering from IBD.

In conclusion, our study aims to address critical knowledge gaps in IBD research and contribute to the field by utilizing the IBD Plexus data to enhance our understanding of stem cell regulation in IBD and its potential clinical applications. We believe that our research has the potential to make a significant contribution to the field of IBD and advance our understanding of this complex disease. Which in turn would improve IBD patient’s life first as children and after as adults."

Opportunities for a student

The student will acquire foundational bioinformatics skills without needing any prior knowledge or coding experience.

They will learn to handle raw data and apply bioinformatics tools for standard RNA-seq and single-cell RNA-seq analyses. This enables them to navigate complex biological datasets, ensuring proficiency in data processing and interpretation.

In addition, the student will also receive hands-on training in establishing 3D organoid models from patient samples including expansion, maintenance, and storage techniques. This holistic approach ensures understanding of both computational and experimental aspects of modern biological research.

This training program is designed for accessibility, making it suitable for students from diverse academic backgrounds. By the end of the project, the student will possess a robust skill set, enabling them to confidently handle intricate molecular data, conduct advanced analyses, and apply their knowledge to real-world biological questions.

Project host statement:

Dr Brinda Balasubramanian

"As an early career researcher, I am deeply motivated to host a BVS student over the summer. Having mentored numerous bachelor's, master's, and PhD students during their thesis research, I am confident in by abilities to formally supervise a student. My journey of self-taught bioinformatics has equipped me with a unique perspective, enabling me to teach this in a way that is clear, engaging, and free from overwhelming complexities.

I am optimistic about the future of bioinformatics and its collaboration with non-animal models like organoids, which represent the forefront of scientific research. Introducing students to these techniques early on will not only enhance their skills but also provide a robust foundation for their future careers. By hosting a BVS student, I am dedicated to nurturing their potential, fostering a passion for these advanced methodologies, and empowering them to contribute meaningfully to the scientific community."

This project can be offered on a part-time basis.

Details of anyone else who will be involved in the supervision of the student for this project.

Paloma Ordonez Moran (Principal Investigator of this project)

Scientific areas: 

• complexities of human health and disease, including clinical and population-based approaches

Background:

Brain tumours are among the leading causes of cancer-related deaths in children. While surgery, radiotherapy and chemotherapy have increased survival rates these tumours still cause many deaths among patients. In addition, many survivors suffer long-term side effects from these treatments.

Thus, greater understanding of the molecular basis of disease in these tumours is needed in order to improve patient treatment and survival.Rab GTPases are a large family of small GTPases that control vesicle budding, motility and fusion in all eukaryotes. Many studies have linked Rab dysfunction with cancer progression and metastasis, although their role in paediatric brain tumour has yet to be defined. In other tumour types, Rab dysfunction is associated with increased protease secretion, growth factor receptor recycling to the plasma membrane and exosome secretion, all of which are linked to poor prognosis and disease progression.

The aim of this project is to test the hypothesis that specific Rab GTPases regulate vesicle trafficking pathways that contribute to the pathogenesis of paediatric brain tumours focusing on ependymoma and high-grade gliomas (including glioblastoma multiforme (GBM), anaplastic astrocytoma and diffuse intrinsic pontine glioma (DIPG))."

Opportunities for a student

The overall scientific training to be received by the student will include:

• cell culture
• molecular cloning
• confocal microscopy
• sub-cellular localisation of molecules
• protein-protein interactions
• bioinformatics
• statistics

Project host statement:

Dr Alistair Hume

"My motivation in providing a project for this scheme comes from my enthusiasm to give students from less represented groups a valuable chance to gain hand on experience in an active research laboratory in order that they  consider this a future career possibility. Currently much of the research in UK Universities is carried out by students from a middle class background and it is essential to meet the needs of society that there is some diversification of the research community. By hosting students I hope that this will pave the way to break down some of the barriers and improve the quality research and speed progress and innovation."

This project can be offered on a part-time basis.

Details of anyone else who will be involved in the supervision of the student for this project.

Deborah Briggs, senior technician and Joseph Allen, PGR student.

Scientific areas: 

• fundamental processes that underpin biology, to understand more about how life works
• development of methodologies, conceptual frameworks, technologies, tools or techniques that could benefit health-related research

Background:

Diatoms are unicellular photosynthetic algae enclosed in porous 3-dimensional (3D) nano patterned silica enclosures called 'frustules'. The diatom frustules are made from biosilica self-assembled into intricate porous shells that feature unique properties including high specific surface area, biocompatibility, tailorable surface chemistry, thermal stability, and high mechanical and chemical resistance. The ability to cultivate diatoms in artificial environments and the abundant availability of diatom frustules as mineable fossilised mineral deposits (diatomite or diatomaceous earth; DE) make diatom silica a promising natural alternative to synthetic porous silica for a broad range of biomedical, environmental, agricultural and energy applications (https://doi.org/10.1002/adhm.201800552).

These Diatoms are well known for the spectacular design of their silica-based cell walls, which can be found in almost every aquatic habitat on earth. They are a major contributor to global carbon fixation as well as the food chain in the marine. More than 10 000 species of diatoms are currently known, and species identification is mainly based on the shape and structure of their silica-based shells. 

One of the most unique aspects of these organisms is how they precisely control silica formation and patterning. The formation of this nanostructured silica is genetically controlled, which implies the participation of defined gene products. The remarkable in-vivo control of the morphology of these intricate structures at small length scales has attracted a great deal of interest in recent years, as these features exceed the capabilities of present-day in-vitro materials engineering. During the last few years, gene products involved in silica biomineralisation in diatoms have been discovered and characterised along with the physicochemical properties of these unique molecules regarding the main aspects of silica precipitation and patterning (https://doi.org/10.1002/adfm.200500616).

The applicants (Advanced Materials) research group has done a lot of work with phosphates (mainly phosphate-based glasses - https://technology.matthey.com/article/63/1/34-42/) with a focus on biomedical applications. More recently, he has been working with colleagues from the Sustainable Process Technologies (SPT) research group, who specialise in biological sciences, chemistry and engineering. The SPT group aims to develop sustainable biomanufacturing processes, generating materials from renewable resources. 

The above groups are working together to explore if porous structures similar to the silica skeletons can be developed from other materials utilising natural resources and processes.

Aims, hypotheses and research question(s) to be addressed:

The aim of this project will be to investigate the influence of incorporating other inorganic materials with diatoms and characterising their effect on diatom skeletal formation. The hypothesis to be explored is that introducing other resorbable glassy materials such as phosphates and borates can influence the skeletal architecture formed by diatoms.

The research questions will focus on:

1. What is the effect of introducing phosphate glasses on diatom skeletal formation?
2. What is the effect of introducing borate glasses on diatom skeletal formation?
3. How does introduction of the above inorganic materials effect skeletal porosity formation?
4. What are the mechanisms of action in these circumstances?

References:
1) Shaheer Maher, Tushar Kumeria, Moom Sin Aw, Dusan Losic. Diatom Silica for Biomedical Applications: Recent Progress and Advances. Advanced Healthcare Materials. Volume 7, Issue 19, 2018: 18005522) M. Sumper and E. Brunner. Learning from Diatoms: Nature's Tools for the Production of Nanostructured Silica. Advanced Functional Materials. Volume 16, Issue 1, 2006: pages 17-263) Ifty Ahmed. Developing Unique Geometries of Phosphate-Based Glasses and their Prospective Biomedical Applications. Johnson M"

Opportunities for a student

The overall scientific training to be received by the student will be split between two groups (AMRG and SPT) to include:

1. How to conduct efficient literature review surveys
2. Training on how to culture diatomic algae
3. Understand the silica skeletal formation mechanisms
4. Understand influencing of skeletal formation mechanisms utilising alternate materials
5. Training on effective characterisation techniques to include, SEM, EDX, XRD, FEG-SEM, FTIR and Raman analyses
6. How to write effective scientific reports
7. Deliver scientific presentation to AMRG (Advanced Materials) and SPT research groups

Project host statement:

Dr Ifty Ahmed

"My motivations for hosting a summer vacation students are to assist them significantly by enhancing their work experience and CV and help them to progress onto the next stage of their careers. This could either include exploring further academic research (ie PhD level studies) or conducing R&D work for industry after they graduate.

I have regularly hosted summer students from the Bioengineering MSc courses at University of Nottingham and have also undertaken supervision of 16-17 year old school/college students through the Nuffield Summer Placement scheme. The aim of this scheme is to entice/encourage young students from underprivileged or disadvantaged backgrounds to go to study at University, by giving them a taster of being at University."

This project can be offered on a part-time basis.

Details of anyone else who will be involved in the supervision of the student for this project.

The student will also be co-supervised by my colleague based in SPT, Dr Samantha Bryan, who is an experienced molecular biologist with microbial biomanufacturing expertise and will lead on microbial biosynthesis and strain development / optimisation aspects. Her labs are equipped with photobioreactors, loop reactor and other bioreactor systems.

My postdoctoral researcher (PDRA) and PhD student will also help to train the student in carrying out H&S assessments and documentation as well as lab-based activities and training.

The student will be placed within my research group and receive their own desk where they will be situated alongside other new summer MSc students who will be starting at the same time. My research group holds weekly meetings where activities, issues and next steps are all evaluated and reviewed.

Scientific areas: 

• fundamental processes that underpin biology, to understand more about how life works
• development of methodologies, conceptual frameworks, technologies, tools or techniques that could benefit health-related research

Background:

Vascular endothelial growth factor (VEGF) is an important mediator for proliferation, angiogenesis and the repair of microvascular networks (e.g. in the heart and kidney) (Peach et al., 2018.  In J Mol Sci 19: 1264). VEGF constitutes a family of mammalian homodimeric glycoprotein members, VEGF-A, VEGF-B, VEGF-C and VEGF-D.  Multiple isoforms of VEGF-A ranging from 111 to 206 amino acids in length can be generated by alternative exon splicing that differ in their ability to bind the glycosaminoglycan heparin and the co-receptor neuropilin-1 (NRP1) and may play distinctive roles in angiogenesis.

We have recently reported on the properties of specific isoforms of VEGF-A binding to VEGFR2 in living cells using a novel NanoBRET approach (Peach et al., 2018. Cell Chem Biol 25: 1208-1218). VEGF family members bind to three different VEGF receptors (VEGFR1, VEGFR2 and VEGFR3) with differing selectivity. VEGFR2 is the major regulator of VEGF-driven responses in endothelial cells including permeability, proliferation, invasion and migration.  Its signalling pathways are relatively well understood with tyrosine residues Y1175 and Y1214 in the human VEGFR2 being the main auto-phosphorylation sites activated by VEGF binding. This creates binding sites for key signalling proteins such as Grb2, PLCgamma and SHC. The binding of VEGFs to VEGFRs induces receptor dimerization that leads to a change in the conformation of the intracellular domains and auto- or trans- phosphorylation of specific tyrosine residues of the receptor dimer resulting in the activation of the intracellular signalling cascades mentioned above.

More recently, cross-family ligand-binding and signalling has been suggested for VEGFR2 and platelet-derived growth factor receptors (PDGFRs).  Thus, VEGF-A has been reported to signal through both PDGFR-alpha and PDGFR-beta receptors. whilst PDGF-AA, AB, BB and CC have been shown to bind with high affinity to purified VEGFR2, although it remains to be established what implications this has for VEGFR2 signalling. The PDGF family consists of four different PDGF chains (A–D), which assemble into functional homodimers or a PDGF-AB heterodimer, and two receptors (PDGFR-α and PDGFR-β), which form homo- or hetero-dimers on ligand binding. PDGF-AA binds only PDGFRα, whereas PDGF-BB binds both homodimer and heterodimer PDGFRs. The less abundant PDGF-CC and -DD bind to PDGFR-α and PDGFR-β homodimers respectively, and both bind to the PDGFR-αβ heterodimer. PDGF-C and -D are structurally more similar than PDGF-A and B to the VEGF family.

There is therefore an urgent need to evaluate in detail the molecular pharmacology of cross-family ligand binding of VEGFs and PDGFs to PDGFRs and VEGFR2.  This requires highly sensitive techniques that can be undertaken in living cells at the extremely low expression levels found in native cells. Over the last few years, we have developed a novel binding assay to study VEGF isoform binding to VEGFR2 and NRP1 in real time in living cells.  This involved the generation of fluorescent VEGF-A isoforms labelled with tetramethylrhodamine (TMR) to investigate ligand binding to VEGFR2 and NRP1 using Bioluminescence Resonance Energy Transfer (BRET) (Peach et al., 2018. Cell Chem Biol 25: 1208-1218). We have also used a similar approach with fluorescent ligands to study ligand-binding to GPCRs and the interleukin 23 receptor [Stoddart et al. 2020. Commun Biol 3:722; Lay et al., 2023 Nature Commun 14:2882]. We tagged the N-terminus of VEGFR2 or NRP1 with the extremely bright 19 kDa NanoLuciferase (NanoLuc). This can excite a nearby fluorophore in close proximity (<10 nm), such as a fluorescent ligand bound at the receptor’s orthosteric site (e.g. VEGF165a-TMR or VEGFR121a-TMR). In this project, we will use these fluorescent probes to study their binding to the two PDGFRs. We will also generate a fluorescent variant of PDGF-AA and study its binding to VEGFR2.

Opportunities for a student

The successful student will join a vibrant and multidisciplinary research group with a wide experience of receptor signalling and NanoBRET technologies. The student will learn cell culture, some molecular biology and a number of fluorescent ligand techniques. There is a large cohort of postgraduate student and postdocs within the research group who will be able to support all aspects of the project. 

There is a very positive research environment locally. Members of the team have also been part of the Team Science committee of the Centre of Membranw Proteins and Receptors (COMPARE), driving positive changes in research culture, initiating mentoring programmes and supporting students at all stages of their development.

The student would have a significant amount of support, both from within the immediate team and more broadly within the wider research environment where Team Science is embedded in all activities.

Project host statement:

Professor Stephen Hill

"I am a Professor of Molecular Pharmacology within the School of Life Sciences with a strong interest in drug discovery based on the in-depth study of cell surface receptors. I have considerable experience of training, supporting, developing and mentoring up-and-coming scientists of all ages and from all walks of life.

We have built a strong multidisciplinary and multicultural research team within our research group, where Team Science and fun is embedded into all our activities. As part of their own development, we encourage our postdocs to gain experience of nurturing and developing talented individuals, and hosting a BVS student over the summer fits with this philosophy. If we are successful in recruiting a summer student, I can confirm that they will be exceptionally well supported and have a great deal of fun tackling cutting-edge research problems of relevance to clinical science."

Details of anyone else who will be involved in the supervision of the student for this project.

Dr Simon Platt and Dr Laura Kilpatrick.

Scientific areas: 

• fundamental processes that underpin biology, to understand more about how life works

Background:

The World Health Organization has recognized that there are no safe limits associated with lead exposure. Lead accumulates in body tissues and triggers toxicity and damage to cells, tissues, and organs. Children exposed to lead have neurodevelopmental defects and behavioural abnormalities as well as reduced cognitive functioning and lowered IQ that correlate with blood lead levels. Hence, there is a need to model lead exposure to neurons and consider methods that might protect neurons from damage and neurodegeneration.

Our laboratory has considered the neuroprotective benefits of certain phytochemicals as some display powerful antioxidant properties that are able to counter some of the cellular oxidative stress that is induced by lead.  The project offered will extend this work and consider which phytochemicals provide suitable neuroprotective effects against lead-induced neurotoxicity.

Opportunities for a student

The student will join a dynamic, international, multicultural, clinical toxicology research group.

Training in the cell culture and differentiation of neurons will be undertaken and then assessment of lead-induced neurotoxicity using spectrophotometric assays for cell viability as well as measurements of apoptosis using flow cytometry. 

Pre-incubation of cultured cells with certain phytochemicals will provide a means to evaluate their ability to protect from the induction of lead damage and associated loss of cell viability. 

Lead-induced protein damage and associated neuroprotection will also be evaluated using protein separation techniques and Western blotting. 

The project will be stand-alone but dovetail with other ongoing lab projects and should provide novel data for the student that will contribute to a research publication. The student will therefore benefit from onsite training and working with other PhD students and will be able to develop their scientific independence.

Project host statement:

Dr Wayne Carter

"My undergraduate final year research was my first taster of lab-based research. This enjoyable and rewarding experience was the initial driving force and motivation for my subsequent career as a scientist.  Being exposed to bench research as a second or third-year undergraduate is a unique opportunity to gain valuable skills but also consider if scientific research would be a career you would like to pursue.

I, therefore, think that by providing a supportive learning environment for a summer scholarship, a student can gain precious lab experience but also understand the day-to-day planning and execution of experiments and, if it is right for them, further develop their love for science and life-long learning."

This project can be offered on a part-time basis.

Details of anyone else who will be involved in the supervision of the student for this project.

There are currently seven other PhD students working in the group as well as support from technical staff.  Hence, although I will be around to supervise the student there will also be back up and help from other members of the Clinical Toxicology Research group.

Scientific areas: 

• complexities of human health and disease, including clinical and population-based approaches
• development of methodologies, conceptual frameworks, technologies, tools or techniques that could benefit health-related research

Background:

Cardiopulmonary resuscitation (CPR) is an emergency procedure consisting of chest compressions combined with positive pressure ventilation, intended to restore the flow of oxygenated blood to the brain and heart when cardiac arrest, i.e. the sudden state of circulatory failure due to a loss of cardiac function, occurs. 

In the UK each year, there are more than 30,000 out-of-hospital cardiac arrests (OHCA) where emergency medical services attempt to resuscitate the victim. However, less than 1 in 10 people in the UK survive an OHCA. Obesity is a rising health issue, concerns exist regarding the efficacy of quality compressions for CPR in obese patients and it is associated with an increased risk of OHCA. Obese patients are more prone to difficulties in airway establishment and chest compressions in case of sudden cardiac arrest. [1]

The discrepancy between what is recommended by guidelines and the ‘real world’ of CPR has resulted in a near-low survival rate from cardiac arrest in the past years. Due to the difficulty of conducting clinical trials and due to a poor translation of the results to humans in animal studies, the scientific evidence supporting the full understanding of the pathophysiological state of cardiac arrest and CPR strategies still suffers from important gaps in knowledge. 

Computational modelling offers a fresh, new perspective. Virtual models of patients and pathology are amenable to detailed validation, assuring reproducibility and translation into the human application. Our group developed a highly integrated computational model of the human cardiopulmonary system, namely the Interdisciplinary Collaboration Systems in Medicine (ICSM) simulator [2-4]. We recently used it to identify CPR protocol parameters that optimise the return of spontaneous circulation (ROSC) after cardiac arrest in a cohort of virtual (adult) patients. [5]

Aim and objectives

Using the ICSM simulator, this project aims to determine whether CPR should be optimised for the obese population. The aim will be achieved through the following objectives:

Objective 1: Creation of a bank of obese subjects

The student will conduct a literature search to retrieve the following to describe the cardiovascular and pulmonary systems in obesity:

• cardiovascular and pulmonary parameters (e.g. systemic artery resistance, left and right ventricles elastances, left and right unstressed volumes)
• haemodynamic data (e.g. cardiac output, stroke volume, ejection fraction)
• gas exchanges data (e.g. arterial pressure of oxygen and carbon dioxide, end tidal carbon dioxide) 
• metabolic data (e.g. oxygen consumption) that describe the cardiovascular system in obesity. 

Data will be used to build a bank of virtual obese subjects (5-10 subjects) describing different degrees of obesity (e.g. BMI 30-40 kg/m2).

Objective 2: Global optimisation algorithm to identify the optimal chest compression parameters.

The student will investigate the success of resuscitation through surrogate model outputs. To assess the effectiveness of the CPR strategy, the following model outputs will be evaluated because of their association with the ROSC: coronary perfusion pressure (CPP), cardiac output (CO), cerebral tissue oxygen volume (brainO2), myocardial tissue oxygen volume (heartO2), end-tidal CO2 (ETCO2) and systolic blood pressure (SBP). 

The student will use a genetic algorithm method to solve the optimisation problem to find the sets of chest compression parameters (i.e. chest compression depth, chest compressions per minute and compression ratio, fraction of oxygen) that optimise the CPR model outputs (i.e. CPP, CO, brainO2, heartO2, ETCO2 and SBP) associated with ROSC. 

References

1. Shahreyar M et al. JACC: Clinical Electrophysiology 2017; 3: 174-83
2. Hardman JG et al. Br J Anaesth 1998; 81:327–32.
3. Das A et al. Conf Proc IEEE Eng Med Biol Soc 5319-22
4. Laviola M et al. Br J Anaesth 2019; 122: 395-401
5.Daudre-Vignier et al. Resuscitation 2023; 186: 109758"

Opportunities for a student

Dr. Marianna Laviola (primary supervisor, bioengineer) will provide daily training and education on the use of computational simulation, research methodology and scientific writing.

The student will acquire the following:

• An understanding of computational modelling of human systems as a research tool in Medicine
• An in-depth knowledge of the pathophysiological state of cardiac arrest in obesity and cardiopulmonary resuscitation strategies
• An understanding of computational modelling: a transferable skill with relevance to research and clinical care
• Development of computational modelling skills and tools, using MATLAB software
• Acquisition of transferable research skills (e.g. literature searching, formulating research questions, conducting modelling investigations, interpreting results and discussing results)
• Understanding and skills in interdisciplinary research methodology (i.e. research using Medicine, Bioengineering, Mathematics, Computer Science)
• Academic and scientific presentation and writing skills (the student will present the results of the project through presentations and a short dissertation).

Project host statement:

Dr Mariana Laviola

"I am really excited to host a BSV student because this is a unique opportunity for a student to 'taste' an interdisciplinary research project of this nature, combining Medicine, Bioengineering, Computer Science and Mathematics. This is a fantastic opportunity especially for those new to research, as the requirements do not require you to be familiar with research before.

The project is likely to lead to the publication of at least one abstract. The student undertaking this project is welcome to work flexibly in terms of location and time, if appropriate checks are made with the supervisor and research team and that adequate progress is made.

I have extensive experience supervising doctoral, postgraduate and undergraduate students with different educational backgrounds and I really enjoy supervise. Even though I am an assistant professor, my student career ended not long ago. I have vivid memories of what it means to be a student and its expectations. 

I am confident that at the end of the scholarship, the student will be a curious scientist, develop a passion for biomedical science, and become a more independent learner."

This project can be offered on a part-time basis.

Details of anyone else who will be involved in the supervision of the student for this project.

The student will receive supervision and education from Prof Jonathan G. Hardman (Marianna Laviola’s line manager), who is Professor of Anaesthesia, the Head of the research group, a Consultant Anaesthetist, and the associate Editor-in-Chief of the British Journal of Anaesthesia.

Scientific areas: 

• fundamental processes that underpin biology, to understand more about how life works

Background:

Rubidium (Rb+) is an alkali metal in the same group as potassium (K+). Although it is the 16th most common element in the earth’s crust, it is only present in biological fluids at a thousand-fold lower concentrations, compared with concentrations of K+, with which it shares similar biophysical and chemical properties. Potassium ions (K+) constitute the main intracellular cation with their efflux to the extracellular space resulting in cellular depolarisation and it is plausible the Rb+ may substitute for K+ in certain physiological functions.

Currently, Rb+ has no definitive biological role but observations suggest a link with hypertension, anti-cancer effects and renal sodium reabsorption. Pre-eclampsia (PE; new hypertension in pregnancy with multi-organ system involvement) is one of the main causes of mortality in pregnant woman world-wide. In our pilot work, we documented lower plasma and lower urinary Rb+ in women with both gestational hypertension and PE, in relation to normal pregnancies. Comparison of plasma and urinary concentrations of Rb+ and K+ suggest that Rb+ does not passively follow K+, as has been assumed, and that the systemic handling of Rb+ may differ in PE.

Given the lack of information on any physiological role for Rb+ and its physicochemical and physiological similarities to K+, this project will seek to examine novel effects of Rb+ on cellular and reproductive function. Specifically, the hypothesis to be tested during this laboratory study is that Rb+ differentially modulates cellular function in cells of the human placenta of normal and pre-eclamptic pregnancies.

The aims of the project are:

1. to compare the effect of Rb+ on permeability of cells isolated from the placentae of normal and pre-eclamptic women
2. to test the effects of rubidium in the presence of K+ transport modulators to determine whether Rb+ utilises similar pathways to K+ in eliciting its effects.

Methods to be used include cell culture of placental cell lines or derived from fresh samples, fluorescence-based assays and electrical measurements of cell permeability to compare the underlying the actions of Rb+ with K+. We will use cultured placental cells maintained within transwells until they develop into a monolayer. The cells will then be stimulated with varying concentrations of Rb+ and K+ and we will assess permeability via the passage of fluorescence markers through the cell monolayer. 

We will also use the technique of transepithelial electrical resistance (TEER) to correlate changes in permeability with altered electrical resistance and to determine whether blockers of K+ transport pathways, added to the culture media, also alter Rb+-mediated ion fluxes. The project will provide an excellent opportunity to work with an enthusiastic and experienced team based in the Medical School at the Royal Derby Hospital.

No prior experience in any of the methods mentioned is necessary.(For this project, you will need to be vaccinated against Hepatitis B due to the work with human tissue samples, which will be arranged for you if required).

Opportunities for a student

The student will undertake a research training programme over 8 weeks comprising specific experimental methods and transferable skills which will introduce them to the possibility of a future career in research. The bespoke training programme will cover week by week activities and expected outcomes. A training record will be maintained by the student to chart their progress and activities undertaken e.g. lab induction, health and safety awareness, practical skills, use of lab equipment etc.

Training will be provided in a range of cell-based assays and cell culture focusing also on data generation and data analysis. These are skills in demand by industry and for studying for a higher degree.  Mentoring of the student by the supervisors will be an important component of the training underpinned by regular meetings to review progress and development.

Communication, dissemination and networking will be strongly encouraged through attendance and presentation at local lab meetings to share and present their project findings to other scientists. This will help build confidence and develop familiarity with scientific terminology.  

Project host statement:

Professor Raheela Khan

"Progress in research requires alternative perspectives drawing from a diverse talent pool and to ensure that research is inclusive, reflecting the communities it serves. By targeting underrepresented groups, the WBVS scheme enables involvement with science at a key stage during a degree providing insight and experience of working in an active research lab.

Having diverse role models is essential in order to be relatable and to highlight that a scientific career is a viable choice, irrespective of background. My lived experience means I am familiar with many of the challenges encountered in building a scientific career. My research interests in human pregnancy stem from tackling inequalities, to deliver equitable solutions to improving healthcare for all and communicating the need for diversity and inclusivity in research design.

Hosting you in our team which enjoys close links with the NHS for recruitment to our studies, you will engage in exciting research, receive tailored training and gain experience to help inform your future career aspirations."

Details of anyone else who will be involved in the supervision of the student for this project.

Dr Vic Sun, Technician.

Scientific areas: 

• development of methodologies, conceptual frameworks, technologies, tools or techniques that could benefit health-related research

Background:

Non-invasive medical imaging has transformed neuroscientific discovery and clinical practice, providing a window into the human brain.

Magnetic Resonance Imaging (MRI) scanner are used to obtain images of the human body (including organs, bones, muscles and blood vessels) in a noninvasive way using powerful magnet and radio waves to stimulate hydrogen atoms contained in the water molecule of the body. Structural imaging techniques like generate ever more precise images of the brain, but in many cases, it’s the function within the brain neural networks that underlies disease. To fully understand the brain, we must accurately combine functional and structural data. Functional MRI technique provides one way to obtain functional information, but the long-time scale necessary to acquire data makes it clinical impractical for non-cooperative patients, such as children with epilepsy. 

Therefore, different techniques should be used, such as Electroencephalography (EEG) cap and Magnetoencephalography (MEG) scanner as the electrical currents in brain neural networks generate both electric and magnetic fields. The latter pass through the skull and can be measured above the scalp surface using MEG scanner. The new generation of MEG scanner uses sensors called Optically Pumped Magnetometers (OPMs). This offers unique insights into brain electrophysiology, with extremely high temporal resolution. However, OPM-MEG is a functional imaging technique meaning no structural images are acquired. If we want to discern where these magnetic fields originate in the brain (a process called source reconstruction), we must also acquire a structural image (e.g., MRI) and discern the sensor locations and orientations relative to the brain (co-registration). 

This project consists of the development of a new methodology on co-registering an anatomical MRI image of the brain with OPM-MEG sensor locations to improve the localisation of the brain signal. The typical accuracy of co-registration is ~5 millimetre and is hindered by user error– if successful, this technique will greatly reduce user input and bring the accuracy to ~1 mm. 

During the internship, (*) you’ll have the opportunity to work with cutting-edge medical imaging scanners located in the Sir Peter Mansfield Imaging Canter (SPMIC), both MRI and OPM-MEG to acquire data; (*) you’ll will use data acquisition and data analysis software to improve the co-registration and to compare previous and new co-registration results (*) you will improve your experience in team working, programming, and problem solving, and boost your knowledge on various medical imaging techniques. Details of the project will be redefined with you at the beginning of the internship, based on your interest and expectations.

Opportunities for a student

The student will:

• receive trainings on how to operate safely various medical imaging scanner while supervised
• receive a safety training to be allowed in the laboratories
• boost their knowledge on programming and medical imaging
• be included in collaborative and inclusive research groups to experience team working, boosting their confidence on presenting and share scientific results other than networking and socialise with young and senior researchers working at the SPMIC.

Project host statement:

Dr Laura Bortolotti

"I am excited to host a BVS student over summer 2024. I am aware of the impact that these experiences could have on the future choice of undergrad students to whom I can relate as a woman in STEM who accessed funding to cover university fees. I would then care to provide to the students the best experience possible over their period working at SPMIC, other than pastoral support for future choices if requested."

This project can be offered on a part-time basis.

Details of anyone else who will be involved in the supervision of the student for this project.

The project will be co-supervised by Dr. Ryan Hill, research fellow at the SPMIC.

Scientific areas: 

• fundamental processes that underpin biology, to understand more about how life works

Background:

The project aims to unravel the intricate mechanisms underlying cell migration by dissecting the role of specific cytoskeletal components. Cell migration is a fundamental process crucial for various physiological functions, including embryo and tissue development, immune response, and wound healing. Although cell migration is widespread in animal development and homeostasis, the signals that direct cells and the machinery within cells that allows them to move is highly variable. Indeed, some cells show plasticity in their mode of migration whilst other cells do not.  Understanding the essential cytoskeletal elements governing cell movement is pivotal for advancing our knowledge of cellular dynamics and potentially unveiling novel therapeutic targets for various diseases.

Our lab studies the primordial germ cells (PGCs) of the fruit fly, Drosophila melanogaster, as a model to understand cell migration. PGCs are the cells that will give rise to sperm and egg in the adult, but in many species, including Drosophila, PGCs must migrate during embryogenesis to reach the gonad1. This migration is essential as without it the resulting adult would be sterile.  Whilst we know about many of the molecules that regulate the direction of PGC migration, our knowledge of which cytoskeletal components PGCs use is much more limited. This project will therefore seek to define which cytoskeletal components are essential for PGC migration and to what extent PGCs show plasticity in their ability to use multiple modes of migration.

The student will perform Drosophila genetic crosses to produce embryos in which the PGCs artificially express one of a number of mutant versions of various cytoskeletal components and regulators. The student would then fix and perform immunostaining to detect the PGCs before imaging on a fluorescence microscope. The student will then score the numbers of PGCs mis-migrating in the experimental samples versus controls. The student will then apply suitable statistical tests to see if there are significant differences.

For those cytoskeletal components and regulators that cause PGCs to mis-migrate the student will try to ascertain the reasons behind this by looking at the PGCs mis-migrating in living embryos. We have Drosophila lines that express a green fluorescent protein in PGCs and we can express the mutant versions of the cytoskeletal component/regulator in these embryos and record them live. We can then examine PGC trajectory, speed and morphology as they migrate.

The project's findings may have implications for various fields, including medicine, drug development, and tissue engineering. By elucidating the cytoskeletal components essential for cell migration, this research may pave the way for innovative approaches to modulate cellular behaviour in health and disease.

Opportunities for a student

Practical skills: The student will Drosophila husbandry and genetics including the use of the UAS Gal4 system for mis-expression of proteins in PGCs. The student will become fully competent in immunostaining and fluorescent microscopy and gain experience in live imaging using confocal microscopy. 

Scientific and organisational skills: The student will plan out and execute experiments, record the raw observations, analyse them with appropriate statistical tests and make appropriate conclusions.   

Presentation skills: The student will be given experience in preparing and delivering two presentations. The first will be a journal club (jointly with a PhD student/postdoc) and the second will be a lab meeting with informal feedback given after both presentations to develop presentation skills.

Project host statement:

Dr Andrew Renault

"The central focus of my lab over the last 10 or so years has been asking what signals control the migration and survival of Drosophila primordial germ cells (PGCs). This project represents a new angle on this theme, looking not at the signals themselves but instead at what is downstream of these in the PGCs. The student will therefore be at the cutting edge of the research in my lab and hopefully producing data that would be sufficient to put into a grant application to fund this avenue further. I have hosted summer students, including a Wellcome Biomedical vacation scholarship, in previous years and found it to be very rewarding. 

My lab benefits because we get to do some ‘blue skies’ experiments, whilst the student benefits from some genuine research experience. The latter is very different to say a 3rd year research project due to the more immersive, full time and personal experience. "

Details of anyone else who will be involved in the supervision of the student for this project.

There is a technician in the lab and PGR student who would be able to provide additional support.

Scientific areas: 

• fundamental processes that underpin biology, to understand more about how life works

Background:

Working memory, our ability to hold information briefly in mind when it is no longer in the environment, is a critical cognitive function that underpins flexible intelligent behaviour. Working memory depends on the interplay of a distributed network of brain areas. How these brain areas communicate for successful memory is still under debate. One proposal is that memory-relevant brain areas synchronize especially when information in working memory needs to be updated, re-evaluated, or transferred so it can control behaviour.

Working memory declines drastically as we age. The reason for this is still unclear. One proposal we will investigate here is whether reduced synchrony between brain areas in ageing makes working memory less flexible.

This 8-week project, jointly supervised by JeYoung Jung and Nicholas Myers, will begin to examine this question by testing the causal role of brain rhythms in the controlled access of working memory contents. Recent research has found that neural synchronization in particular frequencies (~2-6Hz) predicts both successful updating of working memory contents, successful representation of those contents at a neural level, and successful behaviour (ref. 1). However, much of this work has been correlational, so the causal relevance is not clear. In this project you will examine whether inducing these rhythms through transcranial alternating current stimulation (tACS) can increase our ability to update working memory by causally affecting brain rhythms (measured concurrently with electroencephalography, EEG). You will use a new working memory updating task (ref. 2) and learn to use neurostimulation and neural recording techniques in humans.

Week 1: Piloting new working memory task, training in tACS and EEG, literature review

Weeks 2-6: Data acquisition, further training in tACS, EEG preprocessing and analysis, and behavioural analysis

Weeks 7-8: Final analysis of data, give lab presentation and begin write-up of findings

References
1. Vries, I. E. J. de, Slagter, H. A., & Olivers, C. N. L. (2020). Oscillatory Control over Representational States in Working Memory. Trends in Cognitive Sciences, 24(2), 150–162. https://doi.org/10.1016/j.tics.2019.11.0062. Muhle-Karbe, P. S., Myers, N. E., & Stokes, M. G. (2021). A Hierarchy of Functional States in Working Memory. The Journal of Neuroscience, 41(20), 4461–4475. https://doi.org/10.1523/JNEUROSCI.3104-20.2021"

Opportunities for a student

The student will be fully embedded in the labs of the two supervisors and will participate in lab activities outside their research project.

The aim is to go beyond training in neuroscientific techniques and support the student in identifying and pursuing their interests as a scientist. They will receive hands-on training in state-of-the-art techniques for the manipulation and analysis of brain rhythms. This will include learning about safety and application of tACS, EEG signal processing, time-frequency analysis, and pattern analysis, and how to interpret these signals statistically.

They will learn how to use sophisticated cognitive phenotyping to assess how the causal manipulation affects behaviour. The student will also take part in lab life. The labs run weekly meetings, a journal club, and a book club. These events will allow them to present their project and findings, present and discuss the current state of the literature, and engage in other students’ research projects.

Project host statement:

Dr Nicholas Myers

"We are committed to supporting and training the next generation of talented scientists. We have hosted summer students on a similar scheme recently (BBSRC Magnify) and see this as an opportunity for young scientists to gain experience but also to expand their professional and mentoring network. We want to help you identify next steps and ensure that the work during the project aligns with your career and academic goals. We also see the supervisor role as a long-term commitment, with the offer of mentorship and support extended beyond the duration of the scholarship. This is also an excellent opportunity for our research groups. The supervisors and other group members will benefit from a talented and motivated student in many ways, from gaining suggestions for our research to new perspectives on how we can make our lab culture more supportive and inclusive.

This project can be offered on a part-time basis.

Details of anyone else who will be involved in the supervision of the student for this project.

JeYoung Jung, Assistant Professor (School of Psychology, University of Nottingham), is an expert on brain stimulation, neuroimaging, memory, and ageing. Dr Jung will be a joint supervisor and the student will be equally integrated in the research groups of both supervisors.

Scientific areas: 

• fundamental processes that underpin biology, to understand more about how life works

• complexities of human health and disease, including clinical and population-based approaches

• development of methodologies, conceptual frameworks, technologies, tools or techniques that could benefit health-related research

Background:

Inflammatory bowel disease (IBD) encompasses two conditions, namely Crohn's disease and ulcerative colitis, that present significant health challenges. These diseases have an inflammatory profile and involve interactions between the innate and adaptive immune systems and the intestinal wall. In health, a balance exists between these components, but this can be disrupted, leading to durable alterations in the intestinal microbiome (dysbiosis), disrupted barrier function (leaky gut), and immune system activation (inflammation).

The proposed vacation-scholarship project will adapt an existing mathematical model (developed by the proposed supervisor and collaborators as part of a multi-institutional MRC-funded research programme) that captures the interactions between the adaptive immune system, the intestinal wall and the microbiome. The aim will be to extend this model (which comprises a system of nonlinear ordinary differential equations (ODEs)) by incorporating additional components such as those of the adaptive immune system and those specifically relevant to IBD; these include the inflammatory destruction of the tissue surrounding the site of inflammation and the roles of cytokines and growth factors, such as transforming growth factor (TGF-β), that stimulate cells resulting in intestinal fibrosis. These additions are crucial for a more comprehensive representation of the disease's biological complexity, this complexity of course necessitating that the models embody only the simplest appropriate mechanistic descriptions. The expanded model will enable the more well-grounded simulation and analysis of the dynamic behaviour of the immune system in the context of IBD.

The modified model will be solved numerically, the results being compared to known biological outcomes. Furthermore, dynamical-systems approaches will be implemented to supplement and enhance the understanding developed from the numerical computations - in this regard the role of bistability (referring to systems able to exhibit two stable states) is of particular significance here since, in the context of the immune system, such an analysis could aid understanding of how the system can exist in either a healthy state or a diseased state (as in IBD); moreover, it may provide insight into the factors that might cause a switch between these states.Hence the objective of the programme will be to apply a variety of mathematical methodologies to clarify the triggers of disease onset and progression, and potentially suggest new therapeutic targets.

In summary, this project aims to increase our understanding of how dysregulation of the innate and adaptive immune system can contribute to IBD by building upon an existing ODE model, enriching it with new components, and employing a combination of numerical computation and dynamical-systems analysis with a focus on bistability.

The programme of work will, in brief, comprise the following:

1. Acquire basic familiarity with IBD and of the relevant modelling literature.
2. Construct numerical simulations of the existing model to provide confidence in the numerical approach.
3. Include the additional components in the model and implement extensive numerical simulations to assess parametric dependencies and identify multistable regions.
4. Implement dynamical-systems approaches guided by, and in iteration with, (iii).
5. Throughout, maintain a detailed report, in particular to enable subsequent journal submission if appropriate.

Opportunities for a student

The student will be expected to have a background typical of an undergraduate degree with a significant mathematical component, but will both gain (more) familiarity with a range of mathematical methodologies (scientific computation and nonlinear dynamical systems) and, most importantly, experience in the development of mechanistic models that seek adequately to incorporate aspects of biological complexity: the latter is best acquired through such hands-on research projects and would stand the student in good stead for subsequent work in quantitative biology.

The student would also acquire understanding of an area with significant health implications, such studies often providing strong motivation to those often unfamiliar with such topics. 

Project host statement:

Professor John King

"Mathematical methods are finding increasing application in the biomedical sciences, but there are many important areas that have not be substantively investigated by such approaches. The current project involves one such – namely the role of the immune system inflammatory bowel disease – that seems well-suited to study through the application of the techniques of nonlinear mathematics.

I should therefore relish the opportunity to supervise the project, providing training in methods that could usefully be applied across a broad range of biomedical fields and in turn learning from having a fresh pair of eyes devoted to the subject."

This project can be offered on a part-time basis.

Scientific areas: 

• complexities of human health and disease, including clinical and population-based approaches

Background:

Environmental pollution is a major source of health risk. Recent findings have linked air pollution to neurodegenerative diseases (1). Higher levels of amyloid beta have been found in brains of people exposed to air pollution (2). Air pollution and exposure to heavy metals cause neuronal inflammation, oxidative stress, microglial activation, and changes in the blood-brain barrier (1).

All these can result in cognitive impairment and memory loss. Natural antioxidants such as curcumin and melatonin are being actively researched for their neuroprotective properties. Studies have shown that melatonin reduces pollutant-induced Tau protein hyperphosphorylation (3). 
Melatonin is a hormone secreted by the pineal gland in the brain which mediates several physiological functions that include regulation of circadian rhythm, sleep-wake cycle, and body temperature (4). Melatonin production decreases with age and this decrease is now being associated to age-related sleep-wake disorders and neurodegenerative diseases (4). Melatonin also has anti-inflammatory and antioxidant properties. Several reports have suggested that melatonin can be an important drug target for treating neurodegenerative diseases (3). 
With this background, this study is aimed i) to establish a toxicity model using SH-SY5Y neuroblastoma cells and ii) to characterize the neuroprotective activity of melatonin using this model.

Cell toxicity models serve as important tools to study inflammation associated with neurodegeneration. Lipopolysaccharide (LPS) is an endotoxin that is widely used to induce inflammation (5).

In this study, LPS will be added to SH-SY5Y to induce inflammation and cell viability assays will be used to study the neuroprotective effects of melatonin. The underlying mechanisms by which melatonin exerts its neuroprotective functions are not well-characterized. Previous studies have shown that melatonin regulates Brain-derived neurotrophic factor (BDNF) levels (6). BDNF expression levels will be studied in our model system using western blot assay. Proteins involved in neurogenesis such as synapsinII and doublecortin will also be investigated.

Findings of these studies will be will be an important step towards characterization of melatonin signalling pathways in neuroprotection. Understanding these signalling pathways is crucial to determine the usefulness of melatonin as a potential drug candidate.

References
1. Nabi M, Tabassum N. Role of Environmental Toxicants on Neurodegenerative Disorders. Front Toxicol. 2022 May 11;4:837579. doi: 10.3389/ftox.2022.837579. PMID: 35647576; PMCID: PMC9131020.
2. Hajat A, Park C, Adam C, Fitzpatrick AL, Ilango SD, Leary C, Libby T, Lopez O, Semmens EO, Kaufman JD. Air pollution and plasma amyloid beta in a cohort of older adults: Evidence from the Ginkgo Evaluation of Memory study. Environ Int. 2023 Feb;172:107800. doi: 10.1016/j.envint.2023.107800. Epub 2023 Feb 4. PMID: 36773564; PMCID: PMC9974914.
3. Asefy Z, Khusro A, Mammadova S, Hoseinnejhad S, Eftekhari A, Alghamdi S, Dablool AS, Almehmadi M, Kazemi E, Sahibzada MUK. Melatonin hormone as a therapeutic weapon against neurodegenerative diseases. Cell Mol Biol (Noisy-le-grand). 2021 Nov 25;67(3):99-106. doi: 10.14715/cmb/2021.67.3.13. PMID: 34933727.
4. Campos Costa I, Nogueira Carvalho H, Fernandes L. Aging, circadian rhythms and depressive disorders: a review. Am J Neurodegener Dis. 2013 Nov 29;2(4):228-46. PMID: 24319642; PMCID: PMC3852564.
5. Sangchart, P.; Panyatip, P.; Damrongrungruang, T.; Priprem, A.; Mahakunakorn, P.; Puthongking, P. Anti-Inflammatory Comparison of Melatonin and Its Bromobenzoylamide Derivatives in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells and Croton Oil-Induced Mice Ear Edema. Molecules 2021, 26, 4285. https://doi.org/10.3390/molecules26144285
6. Shokri-Mashhadi N, Darand M, Rouhani MH, Yahay M, Feltham BA, Saraf-Bank S. Effects of melatonin supplementation on BDNF con"

Opportunities for a student

The project will help the student to gain a deeper understanding of health and disease, and more specifically the disorders of the central nervous system (CNS). This project will require the student to actively read and critique current literature which will improve the understanding of scientific literature. The training will aid in the development of laboratory skills, analytical and transferable skills which will be beneficial for the student in career progression as well as in application for graduate schools. I aim to use this program to instil confidence in students so that they can think independently and come up with innovative ideas.

Dr. Arundhati Ray is a neurobiologist and will provide training in research methods used in neuroscience, data analysis and scientific writing. The student will achieve the following skills during the 8-week training program:

• Gain an in-depth knowledge of the pathology of the neurodegenerative diseases and current treatment strategies and limitations
• Develop understanding of the model systems used in neurodegenerative disease research
• Acquire hands on experience in commonly used laboratory techniques such as cell culture and biochemical techniques used in biomedical sciences
• Develop transferable skills such as reading and critiquing scientific literature, data analyses using statistical tools, and results interpretation and discussion
• Develop presentation and writing skills; student will present research findings in the form of presentations and a written report.    

The training will aid in the development of laboratory skills, analytical and transferable skills which will be beneficial for the student in career progression as well as in application for application for postgraduate study.

Project host statement:

Dr Arundhati Ray

"I am delighted to apply for a project for the Wellcome Trust Biomedical Vacation Scholarship. My interest in this position stems from my mentorship role in the Yale University Biomedical Science Training and Enrichment Program (BioSTEP). Yale BioSTEP aims to provide high quality research experience to students under-represented in Biomedical Sciences and help them develop skills and knowledge for their future scientific careers. In Coventry University, I was the Nuffield Scheme Coordinator and have mentored students from underrepresented and disadvantaged backgrounds.

I would like to use this program to support diversity in STEM fields through my experience of mentoring students from underrepresented and disadvantaged backgrounds. With my research experience and interest in cutting-edge science technologies, I’d like to provide research-focused mentoring to foster scientific identity.

My main goal through this role would be to make STEM education accessible to all students, build connections with schools and other universities and most importantly build confidence in students and inspire them to carve their career pathways."

Details of anyone else who will be involved in the supervision of the student for this project.

Dr. Wayne Carter, Associate Professor, Faculty of Medicine & Health Sciences and Dr. Shahida Mallah, Assistant Professor, Pharmacology Technical staff at University of Nottingham Medical School, Derby