Mrc Impact PhD Training Partnership at The University of Nottingham

A new opening PhD position in mathematics is available at The University of Nottingham, UK. The initial contract for this position is 5 years. Applicants should apply before January 17, 2020.

Applications are now open for a range of exciting projects to study Complex Disease for a September 2020 start.

Interviews will take place the week commencing 17 February 2020.

Application details are on the MRC IMPACT DTP website.

The studentships will commence in October 2020, and a stipend (15,009 for 2019/20) and fee waiver for 3.5 years is available for UK applicants, plus research training support grant, travel and laptop allowance.

Fully funded studentships are available for UK applicants. EU applicants who are able to confirm that they have been resident in the UK for at least three years before October 2020 may also be eligible for a full award. EU students who are not able to prove that they meet the residency criteria may apply for a fees only award.

IMPACT is a DTP funded by the MRC between three academic partners - the Universities of Birmingham, Nottingham and Leicester. Research projects within the DTP are focused around the theme of Complex Disease, which allows doctoral students to benefit from a diverse range of projects and skills within the cohort, stimulating students to think 'outside the box' and perform innovative, world-leading research. The DTP also provides the opportunity for students to benefit from the expertise of our research partner, the Research Complex at Harwell.

Translation of novel polymer anti-bacterial coating to invasive medical devices used in the neonatal intensive care for high risk preterm infants

Summary: Infections in premature babies are a leading cause of death, severe illness and are associated with poor long-term outcomes for survivors. Premature babies on intensive care units acquire these infections whilst in hospital, often from their life-supporting medical devices. This studentship will develop new coatings for these devices that resist bacterial colonisation and so reduce the risk of infection in these vulnerable babies. Based in the world-leading School of Pharmacy at the University of Nottingham, in partnership with academic neonatologists in the School of Medicine, the student will develop the new coatings, test them in vitro and in vivo, working closely with our industrial collaborator. There will be opportunities to train at the Harwell Research Complex learning cutting edge skills and spend time in the hospital environment, in a large research-active neonatal intensive care unit, to better understand the clinical need. This PhD will suit a highly ambitious science graduate, in the field of biology or chemistry, who wishes to undertake a truly translational clinical project with industry collaboration and training. It is expected that at the end of the project, the student will be well placed to secure follow-on funding for clinical trials and on-going development or commercialisation.

The efficacy of a leucine-enriched whey protein for improving muscle health in older adults

PIs Professor Philip J Atherton, School of Medicine, University of Nottingham, Dr Bethan E Phillips University of Nottingham and Dr Leigh Breen University of Birmingham.

Summary: By as soon as next year, 20% of the UK population will be over the age of 65-years, dramatically increasing pressures upon health and social care. Muscle mass is a strong predictor of healthy ageing and longevity, with maintenance of this controlled via a dynamic equilibrium between muscle protein synthesis (MPS) and breakdown (MPB). We know that ageing is associated with a progressive loss of muscle mass and function due to a complex, incipient disease known as sarcopenia which begins mid-life; however, the full underlying aetiology of this condition is not yet known. One known contributor to the development of sarcopenia is the "anabolic resistance" of skeletal muscle with advancing chronological age, whereby older muscle is not able to mount the same anabolic, or "maintenance" responses to key anabolic stimuli (namely amino acid nutrition and contractile activity) as in youth. Given the large potential health and societal impact of strategies to prevent or attenuate sarcopenia, this studentship, as a joint venture between the UoN, UoB and AFI, will aim to determine the efficacy of a novel protein supplement for overcoming anabolic resistance, as both a stand-alone strategy and as an adjuvant to resistance exercise training

PIs Paloma Ordez-Morn, School of Medicine and Abdolrahman Shams Nateri University of Nottingham

Summary: Aberrant activation of some pathways can create hierarchically organized tumour tissues where a subpopulation of self-renewing cancer stem cells sustain the long-term clonal maintenance of the neoplasm. These cells have proven to be resistant to conventional therapy and to be responsible for tumour relapse. Our objective is to target these cells based on their stem-like properties and thereby identify efficient approaches for cancer therapies to improve patient survival. I have recently described that differentiating cancer stem cells inhibits colorectal cancer progression (Ordez-Morn et al., 2015). Thus, our student will study the key players which govern the balance between stem cell maintenance and differentiation in colon cancer. To this end, we will use a modified yeast two hybrid system, mouse models, clinical association analyses, high-throughput approaches, single cell technologies, patient-derived material and 3D organoids. The practical goals of our research are to understand how cell fates can be manipulated for inducing cancer cell differentiation. Our results will help to increase patient's response to treatment with target-directed therapy.

Summary: Pneumonic plague is the deadliest manifestation of disease caused by the bacterium Yersinia pestis. Following respiratory exposure in humans, mortality rates are nearly 100% with death in 4-7 days. Its lethality has led to the assignment of Y. pestis as a Tier 1 Select Agent and fears of its weaponisation in bioterrorism.

The aim of this project is to provide a theoretical demonstration that combination therapy strategies, for successful management of the disease, can be guided by mathematical and computational modelling approaches.

The student will develop mathematical models informed by experimental data from the literature, representing the interaction between the bacterium Y. pestis and immune response in the lungs. The effect of antimicrobials, immuno-suppressants, and immuno-stimulants will be simulated providing a prototype capability that facilitates theoretical investigation of optimal treatment strategies and timings based on combination therapy.

This studentship will provide an excellent opportunity to work in an established group at the interface of mathematics, biology and medicine, as well as up to 3 months placement at Dstl (part of the Ministry of Defence). Training in mathematical/computational modelling and statistical inference approaches will be provided throughout the PhD

The induction of beige fat with non-viral gene delivery to treat the metabolic syndrome

PIs Michael Symonds, School of Medicine and James Dixon, University of Nottingham.

Summary: Obesity is a condition of excess fat mass with negative health effects that is very difficult to alleviate. Most dietary interventions have limited effect with ~15% of cases effectively losing weight. Different approaches are required, of which one is to promote energy expenditure. The body contains ~100g of brown fat that when activated can generate ~300 times more heat per gram than any other organ. In addition, there is beige fat that possess brown and white characteristics and can be activated by to produce heat. Enhanced brown/beige fat is thus an effective way to reduce white fat deposition and prevent obesity. A safe way to convert white to brown/beige fat in obese patients would have positive health effects on many conditions including cardiovascular disease and diabetes. We therefore aim to use a novel, safe and cost effective method of gene therapy of a powerful regulatory protein in fat, which can activate brown fat. Converting white into brown fat will be the first step in a pioneering program using genetic medicine to prevent obesity


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