(i) Two Funded PhD positions are available
1. Using cutting-edge imaging techniques to understand how DNA is repaired in vitro and in vivo
Simply stepping outside on a sunny day exposes the skin to enough ultraviolet radiation (UV) to cause blistering and the formation of cancerous tumours. Why this doesn’t occur is due to enzymes present in every cell, which scan DNA for damage and then initiate repair. Xeroderma pigmentosum (XP) is one of a number of diseases caused by deficiencies in this repair pathway and for individuals with XP this leads to skin blistering, cancer and neurological dysfunction. A complete lack of these nucleotide excision repair (NER) enzymes is lethal. Because most organisms are exposed to UV, this mechanism of DNA repair is conserved across all forms of life. In humans over 30 enzymes are involved in NER, whereas in bacteria only 6 enzymes are required. Therefore understanding NER at the simpler bacterial level will provide insight into the human equivalent. Despite decades of research into NER there is surprisingly little known about how the enzymes work together. The main aim of our work is to understand how the bacterial system works as a whole, but still at the molecular level.
Working with the Van Houten group at the University of Pittsburgh, USA this interdisciplinary project will utilize cutting edge imaging and molecular manipulation techniques to define the complete NER pathway in vitro and in live cells. We have recently developed a technology to visualise six fluorophores in wide-field microscopy simultaneously, enabling us to image all of the NER components acting together. This is extremely challenging, but hugely valuable for understanding the complex concert of interactions that occur during DNA repair.
We need an ambitious, dedicated, spirited and intelligent student to engage with this project. This project area is funded by the BBSRC and our lab possesses the complete range of biochemical, cell biological and imaging instruments. In addition, support will be provided by fellow PhD students and a postdoctoral research associate. We have a significant track record of high impact publications, which we aim to achieve within this project as well. Finally, the student will have the opportunity to travel to the USA to meet with collaborators during the project.
2. Developing a novel biomarker for early diagnosis of Parkinson’s disease
Parkinson’s disease is a major cause of morbidity in the UK and affects one in every 500 people. With no cure, and treatments aimed at reducing symptoms, early diagnosis is vital for a better prognosis.
This project aims to develop a novel biomarker technology that will detect single molecules of a-synuclein, the protein associated with Parkinson’s disease. We recently devised a peptide that specifically binds a-synuclein; our aim is to use this peptide to detect the very low levels present in vivo. This will be achieved by engineering the peptide to fluoresce upon its interaction with a-synuclein. Development of a biomarker will go hand-in-hand with the development of single molecule detection technology for the ultimate sensitivity. With this approach we expect to exceed current detection assays by providing a one-step capture detection system with much greater sensitivity. Our ultimate aim is to create a technology that can be installed in clinics for on-the-spot diagnosis.
The development of a high sensitivity biomarker with one-step detection will enable easier and potentially earlier detection of Parkinson’s disease. Early patient diagnosis will help in both personal life and treatment decisions. As drugs with preventative properties become available, their application at an early stage becomes very important. Also, for clinical trials, having an accurate measure of a-synuclein levels in both blood samples and cerebrospinal fluid will permit the efficacy of treatment to be ascertained and accurate progression data for patients identified with this disease.
We work in collaboration with groups at the University of Bath and this project would enable the development of a range of skills from our collaborators and at Kent. This highly innovative project would suit an ambitious student who wants to make a difference to the lives of millions of people worldwide.
(ii) Available self-funded PhD positions
We have a number of on-going projects that could be of interested to a capable, motivated student. If you are interested in joining us on a project or require sponsorship for a project that you feels could work in our lab then please let me know directly. Below are listed a few projects that we are currently recruiting for:
1) Understanding DNA repair in Humans. This project involves working with international collaborators to study the process of DNA repair in Eukaryotes. Compared to bacterial systems this is incredibly complex and challenging. But with our new optical systems we may be able to understand how DNA is repaired in eukaryotes for the first time.
2) Developing a new methodology to measure protein-protein interactions and protein-DNA interactions at the single molecule level. This truly innovative project would involed using laser tweezers, novel nanoprobe devices, DNA tightropes and fluorescent imaging in a concerted effort to investigate the force dimension in these interactions.
3) Molecular mechanisms of heart disease. We have developed a new assay to watch the molecules involved in heart contraction at work. Using this assay there are a huge number of investigations both about disease and fundamental mechanism of heart contraction.
(iii) We are also looking for research fellows
If you're interested in working with me I'm happy to consider supporting appropriate fellowship and studentship applications. Just email me with your project and funding ideas to get the ball rolling. The projects listed for studentships could also be expanded into postdoctoral research projects.
Why work with us?
We are a dynamic and exciting group that is really trying to answer fundamental questions, we are also not afraid to test the canons of science. If you are genuinely excited about science consider joining us.