Split-site Biomedical PhD studentships
The University of Exeter and Nanyang Technological University Singapore (NTU) are world leaders in life sciences research.
NTU is ranked 12th in the QS World University rankings 2018. Attracting top people to NTU is one of four priorities that NTU President Prof Subra Suresh has set out in his latest strategy announcement for the University’s next wave of major growth. A holistic 'Systems Medicine' approach is a defining feature of LKCMedicine research and will be key to its success in maximising impact in a competitive global environment.
The University of Exeter is the UK’s fastest growing and fastest rising research university: between 2006/7-2015/16 the University of Exeter saw the greatest rise in research income compared to other Russell Group universities. Exeter’s Living Systems Institute pioneers novel approaches to understanding diseases and how they can be better diagnosed. This will inform prediction, diagnosis and treatment for some of the most severe diseases facing humanity, spanning a broad spectrum, from chronic neurodegenerative diseases to the animal and plant diseases that threaten food security.
NTU and Exeter are working in partnership to deliver six split-site Biomedical PhD studentships. If successful, you will benefit from expert supervision from researchers in both institutions and have the opportunity to research and live in two great locations, for up to eighteen months in each.
Applications close Thursday 31 January 2019.
The University of Exeter and Nanyang Technological University, Singapore are offering six collaborative postgraduate research projects, with three PhD awards to be conferred by the University of Exeter, and three awards to be conferred by Nanyang Technological University.
The project location and host institution will be determined following the review of applications and based on the criteria below. It is anticipated that all of the projects will involve extended periods spent at both universities.
Project allocation will be based on the applicant’s best fit to a project, following a review of applications submitted to each institution. Applications to undertake the projects at the University of Exeter are open to UK, EU and other international applicants who must meet the entry criteria as set out below, whilst projects hosted at Nanyang Technological University are only open to Singaporean Nationals or Permanent Residents.
All six projects are advertised concurrently at both institutions and three will be allocated to each institution after the deadline has passed, based on a collaborative decision made between the University of Exeter and Nanyang Technological University. The final decision on the successful applicant for each project will be made by the institution hosting the project.
The programme offered at each institution is split-site, therefore students pursuing these postgraduate research projects will benefit from spending time at both Nanyang Technological University and the University of Exeter. Students will spend the majority of their programme at the host institution, and normally between 12-18 months at the partner institution over the course of their research. The duration and number of visits to each institution will be agreed with successful candidates prior to offers being made.
The project location and home institution will determine the regulations that will apply to the successful applicant. The student’s main supervisor will be based at the home institution.
Somatic mutation and regulatory genomic variation in the human brain: relevance to neurodegenerative disease – Assistant Professor Foo Jia Nee (NTU) and Professor Jon Mill (Exeter)
Neurodegenerative diseases represent a major healthcare burden worldwide and the most common cause of morbidity and disability in the elderly. As the population ages, the social and economic burden of these these diseases will increase further.
This PhD project will focus on Alzheimer’s disease (AD), a chronic neurodegenerative disorder that is characterized by progressive cortical neuropathology and cognitive decline, and Parkinson’s disease (PD), a long-term degenerative disorder of the basal ganglia that primarily affects the motor system.
Although the neuropathological signatures of AD and PD are well characterized in post-mortem human brain, the specific mechanisms involved in the onset and progression of these debilitating conditions are still unknown; an improved understanding of these processes is vital to enable the design of effective therapies.
Understanding brain dynamics: merging experiments and models – Professor George Augustine (NTU) and Dr Marc Goodfellow (Exeter)
Healthy brain function is mediated by the coordination of neuronal activity - both locally and across different brain regions - giving rise to large-scale brain dynamics. These dynamics are measured using a variety of techniques, for example magneto-/electro-encephalography or functional MRI in humans, or by fluorescence-based imaging of voltage- or calcium-sensitive indicators in animal models in vivo. Uncovering the nature and mechanisms of large-scale brain dynamics at rest, or during sensory processing, remains a fundamental challenge in neuroscience. In addition to basic insight, improving our understanding of healthy brain dynamics will help us elucidate reasons why abnormal dynamics occur, for example in neurological or neuropsychiatric disorders.
Since brain dynamics emerge and fluctuate in a complex system comprised of many interacting, dynamic components, it is crucial to use mathematical models to assimilate information and to make sense of experimental data. We have very well developed and experimentally validated models and theories for single neurons, but the same cannot be said for models of brain regions. The latter have arisen either from purely theoretical considerations or from results of decades-old experiments, in which electrical stimulation and electrode recordings were used to probe the behaviour of circumscribed regions of tissue. Thus, despite showing promise in applications in health and disease, our models and understanding of large-scale brain dynamics remain rudimentary. However, the last 2 decades have seen significant advances in techniques to probe and observe brain circuits. For example, we can now manipulate and record from specific neuronal populations in vivo with high temporal and spatial resolution, using optogenetics and fluorescent reporters. Thus we are now in a position to improve our basic understanding of brain function by constructing and validating new large-scale theories and models in combination with cutting-edge experimental measurements to test these models.
Sensing and imaging synaptic vesicle trafficking and neurotransmitter release - a novel opto-synaptic interface – Professor Frank Vollmer (Exeter) and Professor George Augustine (NTU)
Whispering Gallery Mode sensors are an advanced optical sensing technology capable of detecting and sizing nanoparticles in the 0.1-500 nm size range. These advanced optical sensing tools have already been utilised for the detection and sizing of Lentiviruses (500 nm) (1), Influenza A virus particles (100 nm) (2), detection of single molecule (1-10 nm) (3) and even single atomic ions (0.1 nm) (4).
This doctoral studentship will enable development of WGM sensors as a novel tool for the detection of neuronal synaptic vesicles (SVs) and the direct detection of synaptic activity at the single-molecule level.
The structure basis of the flavivirus replication process – Assistant Professor Luo Dahai (NTU) and Dr Bertram Daum (Exeter)
Many members of the mosquito-borne flavivirus are well-known human pathogens such as dengue virus (DENV), Japanese encephalitis virus (JEV), West Nile virus (WNV), and yellow fever virus (YFV) and Zika virus (ZIKV). For these positive-sense single-stranded RNA viruses, the RNA replication occurs within a replication complex (RC) that assembles on ER membranes and comprises both non-structural (NS) viral proteins and host cofactors. Several proteins of the RC constitute validated drug targets because of their crucial functions during viral replication. However, a major impediment in developing drugs targeting the DENV RC is that both its structure and composition, the interplay between its molecular constituents as well as the precise molecular mechanisms for viral RNA replication are still elusive. Individual protein components of the RC have been extensively characterized both at the functional and structural level. The proposed study aims to reveal key protein-protein and protein-RNA interactions within the dynamic DENV RC. The knowledge will help the development of specific antivirals drugs and better vaccines against the infectious flaviviruses.
The effect of age and risk of falling on walking: A holistic approach to human movement analysis – Assistant Professor Jia Yi Chow (NTU) and Dr Genevieve Williams (Exeter)
The prevalence of falls among our ageing population presents a huge social and multi-billon dollar challenge to the UK and Singapore in the 21st century. It is estimated that 1 in 3 people older than 65 years fall at least once a year. The human cost of falling is detriment to quality of life and societal contribution through injury and loss of independence. The economic cost associated with these falls is £2.3 billion per year to the NHS. We live in an ageing population; by 2035 it is estimated that 23% of our populations will be over 65 years of age, meaning that the social and economic cost associated with falls will continue to increase. Innovative and scientifically grounded responses to this problem are required. Underpinned by the contemporary dynamical systems theory of motor control this thesis will develop and evaluate novel exercise interventions to provide innovative responses to reducing falls in the elderly.
Initially, the thesis will examine how the dynamics of walking technique differs with age and increased risk of falling. Four participant groups from both sites (18-23, 45-52, and 65-70 years at low-risk and high-risk of falling) will walk while body movements and ground-reaction forces are recorded. Two novel characteristics of walking technique that demonstrate a dynamical-systems approach to movement analysis will be examined. 'Coordination' will capture groups of body segments that move in-time with each other4. 'Smoothness' will be examined via spectral analysis of ground-reaction forces. It is hypothesised that with age and risk of falling fewer coordinated actions will present, and lower-frequency, higher-amplitude ground contacts will occur.
Debugging lung disease: Applying mathematical modelling for a precision medicine approach to the pulmonary microbiome – Assistant Professor Sanjay Chotirmall (NTU) and Professor Krasimira Tsaneva-Atanasova (Exeter)
Understanding how individual people respond to medical therapy is a key facet of improving the odds ratio that interventions will have a positive impact. Reducing the non-responder rate for an intervention or reducing complications associated with a particular treatment is the next stage of for any medical advance. The Precision Medicine Initiative, launched in January 2015, set the stage for enhanced collaboration between researchers and medical professionals to develop next-generation techniques to aid patient treatment and recovery, and increased the opportunity for impactful pre-emptive care. The microbiome plays a crucial role in health and disease, as it influences endocrinology, physiology, and even neurology, altering the outcome of many disease states, including its ability to augment drug response and tolerance.
Therefore, in precision medicine, the focus is on the identification of effective approaches for particular patients based on their genetic, lifestyle and environmental factors. Asian and European phenotypes of respiratory disease and infection are unique and therefore require such precision. While such approaches have been successfully employed to investigate contrasting clinical phenotypes; and by disease trajectories, little is known about ‘precision through microbes’. Precision medicine can be applied to the lung microbiome that includes both bacteria and fungi and their associated metabolic states. These ‘microbial fingerprints’ permit patient stratification and we can identify particular disease phenotypes associated to clinical outcomes potentially amenable to precision and individualised intervention. It is clear that our microbes tell us something about disease, something representing a potential target for clinical intervention.
Nanyang Technological University, Singapore