PhD Opportunity

Defining the role of de novo DNA methylation in the regulation of female fertility

University of St Andrews, School of Medicine, St Andrews, United Kingdom

Applications accepted until opportunity filled

Funded PhD Project (European/UK Students Only)

Project Description

Ovulation disorders are a leading cause of female infertility, present in ~25% of couples who have difficulty conceiving. A women’s fertility is dependent on effectively timing ovulation within a highly-regulated ovarian cycle. A fundamental feature of the ovarian cycle is the synchronization of circadian rhythms driven by a region of the brain called the hypothalamus, in coordination with hormone feedback from the ovaries. It is now becoming clear that DNA modifications (epigenetics) are reversible and exhibit dynamic patterns in the hypothalamus. Our previous work suggests that rhythmic epigenetic changes drive the expression of reproductive hormones in the brain to regulate ovarian cycle plasticity and fertility. However, the specific brain substrates and mechanisms that underlie this control remains poorly understood.

This project aims to bridge a fundamental gap in our knowledge to link epigenetic modifications, circadian timing and the control of female fertility. Using neuroanatomical examination, analysis of gene expression, epigenome sequencing, bioinformatics, physiologic interrogations, and studies of in vivo functional outcomes, the student will identify the epigenetic signals and brain substrates regulating the ovarian cycle. The data generated from this studentship will revolutionise our understanding of non-hormonal; molecular-driven control of reproduction.

The student will gain experience in a range of advanced laboratory techniques that will include sophisticated physiological and whole animal experimentation. Training will be further enhanced by participation in GRADskills, an award-winning skills development programme for researchers. The student will work primarily in Dr Tello’s laboratory, situated in the state-of-the-art Medical and Biological Sciences Building in St Andrews. Dr Tello’s research interfaces cellular biology, pharmacology, and reproductive physiology with the goal of understanding and treating fertility disorders emanating from the brain and pituitary. Dr Stevenson (IBAHCM, University of Glasgow) will be the second supervisor on this project. He will provide specialist knowledge on DNA methylation and assist the student in identifying which gene programs are influenced by changing epigenetic signals.

For further details on the project and informal enquiries please contact Dr Javier Tello on jt65@st-andrews.ac.uk.

A full list of research publications and an overview of the group’s research are available via the University of St Andrews’ School of Medicine website at http://medicine.st-andrews.ac.uk/

Funding Notes

This is a 3 year funded PhD studentships comprising of Home/EU tuition fees and stipend at current research council rates.

John Bradley Clinical Research Programme – Endocrinology

Summer research experience with the John Bradley Clinical Research Programme

 

Over the past summer, Amanda Kung (3rd year BSc student) participated in the John Bradley Clinical Research Programme in Toronto, Ontario.

She was assigned to the Endocrinology department at Michael Garron Hospital, and worked under the supervision of Dr Zoe Lysy, Dr Rebecca Fine, and Dr Raymond Fung. Her research project focused on improving the management of diabetic pregnant patients during the hours of active labour. This involved analysing the data from over 100 patients in order to find areas for improvement in managing this specific cohort of patients.

The programme was six weeks long and consisted of weekly four-hour seminars at the University of Toronto’s Department of Family and Community Medicine. Each seminar focused on a different aspect of research, and students were asked to give one oral presentation to defend their project in the context of that seminar. At the end of the programme, students gave a poster presentation in front of another panel of judges summarising their research and produced a ‘one-minute wonder’, where they were allowed creative freedom to describe their project in a one-minute video.

Amanda recommends this programme to students interested in learning about the various aspects of research and for those wanting to broaden their exposure to clinical research prior to writing their dissertation. She also noted that the programme is the perfect opportunity for students to meet and collaborate with medical students from around the world and make long lasting connections with doctors, professors, and research scientists based in Canada.

International Society for Zinc Biology 2019 meeting and Kyoto Lab Visit

3rd year BHF-funded PhD student Amy Dorward (Pitt lab) and Dr Gavin Robertson (PDRA; Pitt lab) visited Prof Hiroshi Takeshima’s lab at the Graduate School of Pharmaceutical Science, Kyoto University, Japan between 9th August – 14th September 2019. During this time both Amy and Gavin carried out some exciting new experiments, which will contribute to an upcoming publication. They also presented posters at the International Society for Zinc Biology (ISZB) 2019 conference, also in Kyoto.  Gavin was awarded a Metallomics poster prize. Dr Samantha Pitt was invited to give an oral presentation.  Amy was awarded travel grants by Russell Trust, Biochemical Society, British Society for Cell Biology (BSCB) and the School of Medicine.  Gavin obtained funding from BSCB and the Physiological Society.

 

Dorothy Miller bursary presentations: Sharing experiences in Malawi

The three students who were awarded Dorothy Miller Bursaries this year, Sofia Garcia Agudo, Sarah Alvi and Sarah Eshkour, gave great presentations about their experiences in Malawi this summer to an audience of interested second year students and members of staff on Friday 4th October 2019. The session was hosted by Dr Derek Sloan, who gave a background to the Dorothy Miller bursaries, introduced the speakers and facilitated a brief discussion after each presentation.

 

All three students highlighted how much they benefitted from the experience and reflected on some of the challenges they faced. The Dorothy Miller Bursary award is made possible through the generosity of the Miller Family.

 

This year, there was a special guest presentation from Malawian ENT nurse Emily Kwenda. Emily is currently  a Visiting Scholar with the School and is in Fife undertaking training under the banner of the Ungweru Project. The Ungweru Project is a partnership between ENT doctors and nurses in NHS Fife and the School of Medicine. It aims to improve ENT care in Malawi by sharing expertise and knowledge through training.

left to right: Sarah Eshkour, Emily Kwenda, Sarah Alvi, Sofia Garcia Agudo

 

Scotland Malawi Partnership Member Awards 2019

The many threads of the School’s research and teaching activity in Malawi were represented at the Annual Scotland Malawi Partnership Member Awards event, which was held on the 5 September 2019 in Edinburgh’s City Chambers.

The event was presided over by HRH The Princess Royal and attended by 150 Scottish Malawi Partnership members.

The School has a long history of collaboration with the College of Medicine in Malawi, including working with them to develop their curriculum and implementing on online curriculum management system. Members of staff also have an active research and teaching presence in Malawi through the Global Health Initiative, including Prof Stephen Gillespie, Dr Derek Sloan (Infection and Global Health), Dr Bernadette O’Hare (Global Health Implementation and Paediatrics and Child Health) and Dr Andrew Blaikie (Arclight). Our students also have the opportunity to take part in the Dorothy Miller bursary scheme to spend time in Malawi over the summer.

In addition, the School is a partner in the Ungweru project with ENT doctors and nurses in NHS Fife. This project facilitates ENT nurses from Malawi to visit partners in NHS Fife to develop skills and processes to implement in the Queen Elizabeth Hospital in Blantyre. The Malawian nurses are Visiting Scholars at the School  during their time in Fife.

The School was represented at the event by Helen Clark (Assistant School Manager), who reported that it was a day of inspiring presentations, music and an unexpected chat with royalty.

Image credit: : Photographs Kirsty Bain. Courtesy of https://www.scotland-malawipartnership.org/

 

The SMERT project ends in success

Funded by the European and Developing countries Clinical Trials Partnership (EDCTP), the two-year project brought together four institutions in Tanzania: National Institute of Medical Research (NIMR) through its Mbeya Medical Research Centre and National Health Research and Ethics Committee (NatHREC), Kilimanjaro Clinical Research

Institute – Kilimanjaro Christian University Medical College and Tanzania Medicines

and Medical Devises Authority (TMDA), supported by the University of St Andrews (UStAn) as the European partner.

The SMERT team met on 25th on September to prepare for the 2nd and last annual networking forum.

 

On the 26th, the annual networking forum was held at the TMDA headquarters bring together over 50 delegates including representatives of Institutional Research ethics Boards (IRBS) across Tanzania, regional centre of excellence for medicines regulation in Eastern Africa, directorate of vaccines and immunization, policy makers and stakeholders from various agencies in Tanzania. The theme of the forum was, “building Tanzania’s capacity for clinical research and pharmacovigilance”. The conference reflected on the achievements made by SMERT and chart the way forward.

 

 

By its name, SMERT aim was to Streamline health research ethics review and Medicines Regulation in Tanzania. This was achieved in the following ways:

1. Training to equip researchers and members of ethics committees in Tanzania with skills to effectively and timely assess the ethicality of research protocols. This would avoid unnecessary delays in approving research ethics applications and fake research being conducted in Tanzania.  As a result, the median time to approval of research protocols by Institutional Research Ethics boards (IRB) has reduced from 120 days to 32 days.  Bioethics curriculum at was established at Kilimanjaro Christian Medical University College (KCMUCo) to train all postgraduate medical and biological sciences students, and also for continuing professional education.  Two more Tanzanian Universities have adopted the curriculum for training their students.  Furthermore, a short ethics training course curriculum was developed and is hosted by NIMR and after accreditation, NIMR will make the course freely available online as a resource for refresher training of members of research and clinical trial ethics committees across Tanzania. UStAn supported the development of both curricula and Dr Wilber Sabiiti was invited to give a lecture on the ethics- of new frontiers in medical research and responding to public health emergencies to the first class at KCMUCo.

2.  Strengthening infrastructure and human resource for:

Rapid submission, review and feedback of research ethics applications to the NIMR headquarters through NatHREC. To this effect an electronic     system was developed through which research protocols will be submitted, reviewed and feedback given.

Rapid reporting on the safety of medicines and vaccines during clinical trials at TMDA. An electronic system was developed to this effect to expedite reporting of adverse drug events (ADEs) arising during the trial of new medicines. SMERT also supported the enhancement of the system for post registration medicines and increasing awareness of the importance of reporting ADEs by the community. As a result, ADE reporting quadrupled since 2019, the SMERT’s 2nd year of work.

Monitoring ethical conduct of health research and clinical trials of medicines and devices for both NIMR and TMDA. To increase efficiency and cost-effectiveness, joint monitoring visits of research were agreed between NIMR and TMDA.

3.  Harmonising health research ethics review and medicines regulation in the East African community. SMERT achievements on research ethics review will feed into the East African Health Research Commission’s work to harmonise the research ethics review across the East African Community. Through SMERT support, TMDA spearheaded and hosted a forum by all national medicines regulatory bodies to discuss ways for harmonising medicines regulation guidelines across East Africa.

 

The SMERT team held a post-forum meeting on 27th September to discuss the next steps after SMERT phase I.

We believe the long-term impact of SMERT is protecting the people of Tanzania from participating in dangerous research and being tried on with unsafe medicines. Secondly, research participants who get adverse drug reactions during clinical trials will be given the right care within the shortest possible time.

Sir James Mackenzie Institute for Early Diagnosis Launch

Early diagnosis key to survival

 

A new institute, created to help improve earlier diagnosis of cancer, cardiovascular disease, mental health and infection, has been launched at the University of St Andrews.

 

Early diagnosis is key in effective treatment, yet diseases are far more likely to be diagnosed earlier in affluent areas compared to Scotland’s most deprived communities.

 

The Sir James Mackenzie Institute for Early Diagnosis Information is an international collaboration including institutions and researchers from Ireland, Germany, Canada, the Netherlands, the United States and sub-Saharan Africa, sharing knowledge, skills and ideas with the aim of diagnosing diseases to allow for earlier, and more successful treatment.

 

The new Institute will be led by Professor Frank Sullivan of the School of Medicine at the University and will focus on three research areas: Health Data Research led by Professor Colin McCowan of the School of Medicine; Digital Diagnostics and Emerging Technologies led by Dr Peter Caie of the School of Medicine; and Biophotonics in Early Diagnosis led by Professor Kishan Dholakia of the School of Physics and Astronomy.

 

University Principal, Professor Sally Mapstone, said: “Mackenzie was a researcher who made bold decisions, who thought creatively around problems, and who worked in collaboration and across disciplines to find solutions to pressing issues.

 

“The University’s new institute of early diagnosis will draw upon Sir James’s example to inspire and inform our future.”

 

The Institute is named after Scottish cardiologist, Sir James Mackenzie (1853-1925), who invented the original polygraph which revolutionised the diagnosis of heart problems by making simultaneous records of the arterial and venous pulses allowing Mackenzie to identity heartbeat anomalies.

 

The Institute was officially opened on Monday 23 September by the Principal of the University, Professor Sally Mapstone, 100 years after Mackenzie opened his own research institute at St Andrews.

 

The Institute, which will be managed by Karen Hunter, will work with Scottish, UK and local NHS providers and include members of the wider population to create a patient-focused approach.

 

Interdisciplinary collaboration between medicine, biology, computer science, chemistry, geography and sustainable development, and physics and astronomy, as well as mathematics and statistics will be a key tool of the Institute.

 

Sir James Mackenzie was born in Scone, near Perth, studied medicine in Edinburgh and eventually left general practice to specialise in the study of cardiac arrhythmias (heartbeat conditions), moving in 1907 to become a consulting physician.

 

His success led to him being elected as a Fellow of the Royal Society in 1915 and later knighted. He established the Mackenzie Institute of Clinical Research which worked closely with GPs to record symptoms and illnesses of patients and significantly aided scientific development within cardiology.

ENDS

 

 

Contact

Fiona MacLeod

Communications Officer

Tel: 01334 462108

Mobile: 07714 140559

Email: fm43@st-andrews.ac.uk

Press Office: 01334 462530

 

Notes to editors

 

Issued by the University of St Andrews Communications Office.

New blood test trialled on 12,000 Scots catches lung cancer early

Lung cancer is the most common cause of death from cancer in Scotland, with a quarter of all cancer deaths attributed to lung cancer. The current five-year survival rate is approximately 60% for stage I lung cancer but is only 1% for those with stage IV disease. The ECLS study, led by Professor Frank Sullivan, was the largest randomised clinical trial using blood biomarkers for the detection of lung cancer conducted anywhere in the world. It involved 12,209 people who were at elevated risk of lung cancer because of smoking and/or family history. The results showed a 36% reduction in late stage diagnosis after 2 years of follow up for those who received the EarlyCDT Lung test, compared with standard clinical practice. Among those people who received the EarlyCDT Lung test and went on to develop lung cancer within the next two years, 41% were diagnosed at an early stage (stage 1&2) of the disease, compared with 27% among the control group. These landmark findings are likely to have globally significant implications for the early detection of lung cancer by showing how a simple blood test, followed by CT scans, is able to increase the number of patients diagnosed at an earlier stage of the disease, when surgery is still possible and prospects for survival much higher. The next step will be to move to a larger population-based evaluation in up to 200,00 patients to assess the implications of diagnosis with EarlyCDT Lung on survival and mortality in a real-world setting.

 

The trial was sponsored by the University of Dundee and NHS Tayside, and co-funded by grants from Oncimmune Ltd, the test manufacturers, and the Scottish Government Health & Social Care Directorate of the Chief Scientist Office (CSO).

John Bradley Clinical Research Program

Over the summer, third year medical student Janan Illango took part in the John Bradley Clinical Research Program held in Toronto, Canada.

The John Bradley Clinical Research Program has two core components:

  1. a) learning and demonstrating core competencies in applied clinical research methods and
  2. b) completing student-initiated/led research projects

This program provides a unique opportunity to develop an understanding of applied clinical research by working on a supervisor led project in a field of mutual interest.

The program consisted of 34 undergraduate and medical students from Scotland, Canada, the United States, and Ireland.  Each student was matched with a research supervisor to complete a clinical research project over eight weeks.  Janan was matched with Dr. Leung, a geriatrician at Michael Garron Hospital, where he worked on a Quality Improvement study attempting to improve advanced care planning (ACP) documentation at the hospital’s geriatric outpatient clinic. His tasks included analysing patient reports on ACP documentation and creating a code status education program based on feedback from patient questionnaires.

While working on the study, Janan attended seven weekly scholarly sessions held by experts in clinical research, knowledge translation and research ethics. The program culminated with the completion of a “One Minute Wonder” video, a power-point presentation to a panel of experts, a knowledge affirmation assessment and a fun evening of croquet by the beach. It is recommended that medical students looking to gain clinical research experience in Canada join this program next year.

Thank you to the John Bradley Clinical Research Program coordinators, Prof. Sullivan and St. Andrews Medical School for organizing this wonderful applied clinical research opportunity.