Research at the Medical School

Compiled by Divya Manoharan and Deepika Manoharan.

Research, in general, is vital for the development in knowledge and to promote advancements and alterations in our practices. Medical research, in particular, will Screen Shot 2014-07-31 at 2.33.28 PMimpact us all as it is one of the key areas responsible for further understanding the many aspects related to the longevity and well-being of humanity. Imagine dying from a runny nose, not knowing the physiology behind hypertension, living with no cure to malaria, not having a vaccination for polio, or being blind because of no treatment to cataracts. We take most advancements in surgery & medicine for granted and most improvements become a routine part of our day- to-day life, but none of this would have been possible without the world of research which comprises of people with innovative minds, continuously asking questions and digging deeper to find the answers.

The research in our medical school is no different and comprises of a world renowned multi-disciplinary team working in various aspects of medical research ranging in several topics such as molecular medicine, disease mechanisms, community health, ethics, medical education, and psychology. The new building also provides the ideal infrastructure and facilities required by our staff to sustain, develop, and make further accomplishments in medicine.

Some of the research staff were kind enough to take time out of their busy schedule and provided us with some insight on their current and future projects,  interests of study,  and achievements.


 

Professor Gerry Humphris  

Progress in Europe: Health Psychology

Screen Shot 2014-07-31 at 2.34.33 PMSuccessful applications to the Directorate General of Justice and Criminality (European Commission) in 2010 by Humphris, Cecil and Baldacchino with other partners has resulted in innovative research with substantial impact on clinical and young person populations within Europe. The first project which we lead – ORION (Overdose Risk Information Project) – is having its second ‘transnational meeting’  in  Monza on the 28-29th November, 2011. This meeting will tailor the e-health tool (a sub-contracting task for a spin out company associated with University of Keele) for trialling in the Spring of 2012 in Denmark (University of Aarhus), Germany (University of Essen), Italy (University of Bicocca Milano), and of course, Scotland. This is a complex study to manage and we are assisted ably by our own European Office (within RFO) as well as support companies: Synergia (Milan) and Business Solutions Europa (Brussels). The study will be run in our partner organisation – NHS Fife – and require 40 overdose patients to use the e-health tool to inform them about their future risks and Screen Shot 2014-07-31 at 2.33.20 PMwhat they might do to reduce these risks. The study will be completed by February 2013. Visit the ORION website for up to date information (link available on Gerry Humphris’ webpage).

The second project: TRIP (Testing in Recreational-settings prevention-Interventions addressed to Polydrug-users), includes the partners: Bergamo ASL, University of Copenhagen, NHS Fife, and University of St Andrews. This study is an extension of the original ‘Bergamo’ project (2008-2010) which scoped the interventions in reducing illicit polydrug use  in recreational areas (clubs and discos). The original study also designed a menu of intervention approaches and assessment tools. The new project called TRIP is a feasibility project to test the benefits of new interventions in two clubs in Europe (Dundee and Bergamo). The quasi-experimental design will provide the opportunity to explore tentative evidence of effects of the educational intervention (fear appeal and clear instruction of risks). Further study is being planned to gain additional support to roll-out the intervention at a wider set of sites and introduce a cluster-randomised design for clearer interpretation of effects.

Challenges of this research are the close monitoring of activity of all partners, the financial governance demanded by the EU with close attention to maintaining the paper trail and time sheets of work ex- pended. The use of Skype, a good airline timetable and goodwill amongst partners have been essential ingredients to maintain communication and integrate ideas and procedures. These two projects enhance our presence as a research team combining with NHS Fife in clinical and public health relevant activity.


 

Screen Shot 2014-07-31 at 2.35.22 PMDr Silvia Paracchini; Royal Society University Research Fellow

The Genetics of Dyslexia and Neurodevelopment

I have joined the Medical School at the University of St Andrews three months ago appointed as academic fellow. My main research interests are the genetics of childhood disorders, cognition and neurodevelopment. My research program focuses on dyslexia, which is a specific impairment in learning to read affect- ing as many as 10% of children in the UK. While we can blame genes for a significant component in contributing to dyslexia (as much as 70%) with a certain confidence, we are far from understanding exactly which genes can actually be implicated. Identifying these genes will mean to open new investigations to understand what dyslexia actually is and how the underlying biology is determined.

I am part of a multidisciplinary European study, the NeuroDys project, which is aimed at conducting a large genetic screening for dyslexia in a cross-linguistic sample. The recent development in sequencing technology allows comprehensive genetic analysis at an affordable cost at a genome-wide level, in contrast to previous studies which were mainly limited to small genomic regions.

My previous work carried out at University of Oxford has led to identification of one strong candidate gene for dyslexia, namely KIAA0319. I am following up this finding together with reports of other robust candidates to explore how genetic variants linked to dyslexia may influence cognitive traits and reading abilities in the general population. I am conducting this analysis using the ALSPAC cohort (http://www.bristol.ac.uk/alspac/), which is a large longitudinal sample (more than 14,000 individuals) characterised for a large range of cognitive phenotypic measures and for which DNA for genetic analysis is available. The wide range of data available for the ALSPAC cohort combined with the large sample size has the potential to allow gene-gene and gene-environment interaction analysis. I am discussing in more details my research in dyslexia genetics a recent podcast (http://www.ndm.ox.ac.uk/silvia-paracchini-dyslexia-and-genetics).

My most recent work has led to the identification of one of the first genetic association with handedness. We found that genetic variants within the PCSK6 gene are highly significantly correlated with handedness with a very specific effect in people with dyslexia. PCSK6 is a very attractive candidate for handedness because of its known role in establishing left/right body asymmetries in the very early stages of brain development. Understanding the molecular basis of this correlation promises to open new lines of research to further understand handedness, cerebral asymmetries and dyslexia. I have very recently been awarded a 5-year Royal Society University Research Fellowship which will allow me to carry out these studies.

KEY PUBLICATIONS

Scerri TS, Morris AP, Buckingham L-L, Newbury D, Miller L, Ring S, Monaco AP, Golding J, Bishop D, and Paracchini S. (2011) DCDC2, KIAA0319 and CMIP are associated with reading-related traits in AL- SPAC. Biological Psychiatry.

Scerri TS, Brandler WM, Paracchini S, Morris AP, Ring SM, Talcott JB, Stein J, and Monaco AP. (2011) PCSK6 is associated with handedness in individuals with dyslexia. Human Molecular Genetics, 20:608-614


Screen Shot 2014-07-31 at 2.36.20 PM A Programme of Research on Health-related Beliefs, Emotions, and Behaviour

Dr Gozde Ozakinci

Think of a patient who has finished cancer treatment and has been given the all-clear. Imagine how he or she would feel. Elated? Relieved? Ready to get back to their life before cancer? Celebrating with family and friends? These are some of the common reactions we would expect after the end of long and hard cancer treatment. And most people experience them and try to get on with their lives. However, most cancer patients after treatment also experience fears. Specifically, fears about cancer coming back. For some, these fears are transient and they are able to distract them- selves and move on as best as they could. However, for some other patients, that is not always possible. They are affected by the ‘what if’ question more so than some others. ‘What if it comes back? What if it comes back in another part of my body? I’m having lots of headaches/ back pain/stomach pain – what if this means that cancer is now in those parts of my body?’ You can imagine that these are very distress- ing thoughts. They can also affect what a patient might do in response to such thoughts and fears – e.g., seeking help from GP, or oncology staff, ignoring symptoms because of fear that it might be something serious, or making lifestyle changes, etc. (some that might help such as stopping smoking and some may not be so helpful such as taking supplements etc with the hope that it will reduce their recurrence risk). Some of my current projects aim to look at how we can measure these fears in an oncology setting and identify those with high fears so that we can offer them some psychological help to cope with them better and the uncertainty that life after cancer entails. I collaborate with other health psychologist colleagues (Prof. Gerry Humphris) but also surgeons, oncologists, and nurses (Prof. Simon Rogers, Liverpool; Ms. Lyn Wildridge, Edinburgh Cancer Centre).

Think now of someone who feels that modern technology  – mobile phones, power lines, genetically modified food, vaccination programmes can have an adverse effect on our health. Compared to someone who doesn’t have these concerns, we would expect different health behaviours. So, some of my current projects examine what implications these concerns might have on our behaviours. For instance, if people are worried about the negative impact of technology on their health, are they more likely to interpret somatic symptoms in the light of these worries and more likely to seek health care compared to those who don’t have these concerns? Are they more likely to have different health behaviours: e.g. less likely to have daughters vaccinated against HPV, more likely to buy organically grown food, less likely to buy bottled water etc.? So, together with a former postgraduate student (Ms. Kristel King) and research assistants (Ms. Alice Wright and Ms. Ashley Dennis) and my colleagues in Turkey (Dr. Hale Bolak Boratav) and the USA (Dr. Pablo Mora), we look to find answer to some of these questions that have relevance to important health care decisions.

Another recent concern in health care is how we help people change their health behaviours so that they can engage in healthier choices: e.g, better diet, increased physical activity, and stopping smoking. These behaviours are notoriously difficult to change and also once changed, maintain that change. I work with Professor Dave Perrett and our PhD student, Ross Whitehead, to develop and test appearance-based interventions for diet change. We use visual images to demonstrate the physical benefits of diet change to encourage people to eat more healthily. In addition, I’m currently developing projects on how to increase participation in physical activities among cancer patients as well as healthy populations in collaboration with colleagues such as Dr. Anita Laid- law, Dr. Mary Wells (Dundee), Prof. Brian Williams (Stirling) and Dr. Fabio Arico (School of Economics).

These are some of the work that I do in clinical and non-clinical settings that use various methodologies, from survey to interviews to experimental methods. In addition, I am a co-principal investigator in an ESRC-funded project that I’m collaborating with colleagues from various UK universities as well as University of Allahabad examining health related behaviours in Hindu spiritual festival called Magh Mela. But that’s for another time!

SOME RECENT PUBLICATIONS:
Modern health worries, health care utilization, and symptom reporting: Examples from the UK and Turkey Ozakinci, G., Bolak Boratav, H. & Mora, P. Apr-2011 In : Behavioral Medicine. 37, 2, p. 35-41.

Cancer diagnosis: An opportune time to help patients and their families stop smoking?
Ozakinci, G., Wells, M., Williams, B., Munro, A. J. & Donnelly, P. Aug-2010 In: Public Health. 124, 8, p. 479-482.

Appealing to Vanity: Could Seeing Potential Appearance-Gains Motivate Fruit and Vegetable Consumption? (in press). Whitehead, R., Ozakinci, G., Stephen, I. D. & Perrett, D. I. 2011 In : American Journal of Public Health.


Screen Shot 2014-07-31 at 2.50.47 PMDr. Paul Reynolds  

Herding Hippos and Other Strategies in Breast Cancer Research

The Reynolds lab is interested in investigating biological processes and chemical signalling pathways within cells that may have an impact on breast cancer. The ultimate aim is to find novel cellular targets that become future therapeutic drug targets. Current themes include investigating the Hippo pathway, the role of microRNAs and the role of polycomb proteins.

Have you ever considered what controls organ size: what controls how big an organ, such as the liver, can grow before it reaches its limit? Part of the answer is a chemical signalling pathway inside cells called the Hippo pathway. A protein called Willin was originally discovered by Dr. Gunn-Moore while he was investigating rat neuronal cells. Now, a successful collaboration between the Reynolds lab and the Gunn-Moore lab (in Biology) has shown that Willin is a new component of the Hippo pathway.

In experiments using cultured human breast cells, they have found that Willin sends messages (signals) inside cells, via changes in protein phosphorylation, to the protein YAP, which is a gatekeeper for decisions of whether to grow or not. Normally, Willin acts to block the growth-promoting activity of YAP: less Willin activity results in more YAP activity, while more Willin activity results in less YAP activity. When they removed Willin from cells, they observed many cellular features that resembled those seen in cancer cells. Conversely, when they added more Willin, they blocked the cancer-like effects of YAP. This has allowed them to build up a picture of the cellular circuitry and mechanistic links between Willin and the other important components of the Hippo pathway. Future work aims to assess the clinical relevance of the Hippo pathway in human breast cancers.

Much of this work has been carried out by Susana Moleirinho, a PhD student in both the School of Medicine and the School of Biology.

RECENT PUBLICATION:

Angus L, Moleirinho S, Herron LR, Sinha A, Zhang X, Niestrata M, Dholakia K, Prystowsky M, Harvey K, Reynolds PA*, Gunn- Moore FJ* (2011) Willin/FRMD6 Expression Activates the Hippo Signaling Pathway Kinases in Mammals and Antagonizes Oncogenic YAP. Oncogene 30: June 13th (doi:10.1038/onc.2011.224). *Senior authors.


Screen Shot 2014-07-31 at 2.50.27 PMProfessor Andrew Riches

Novel Methods for Detecting Cancer Cells

Early detection of cancer and  follow-up of patients following treatment are key strategies in the fight against cancer. Bladder cancer arises in the transitional epithelium of the bladder lining. Patients often present with haematuria and are thus referred to the Urologists for investigation.  Patients who have been treated for bladder cancer, unfortunately, have a high recurrence rate and thus they have to be followed-up at regular intervals to check for the presence of regrow- ing tumours. Tumour cells are shed into the urine and thus provide an opportunity for screening.

In collaboration with Professor Kishan Dholakia’s group in the School of Physics & Astronomy, we have been developing a technique called Raman spectroscopy to interrogate tumour cells. Electromagnetic radiation, when it interacts with matter, is either absorbed or elastically scattered (Rayleigh scattering) and hence there is no wavelength change. A very small fraction of incident photons (approximately one in 105 – 107 photons) are inelastically scattered, thus resulting in a wavelength change (Raman shift).

Screen Shot 2014-07-31 at 2.32.39 PMThe extent of the Raman shift is a characteristic of the molecules, which the incident beam interacts with. This interaction of the incident photon with the molecule results in an energy exchange and the scattered photon can be of higher or lower energy than the incident photon. This energy change depends on the change in the rotational or vibrational energies of the molecule being interrogated. These vibrational energies are highly specific to a chemical constituent of the molecule and thus provide a signature of that molecule. Thus when a cell is exposed to an incident laser beam of a fixed wavelength, the resultant spectrum of Raman shifts represents a “molecular fingerprint” of the molecules within the cell. This technique has the potential to discriminate between cells with different molecular contents and thus distinguish normal cells from cancer cells.

We have studied a series of human cancer cell lines which we can grow in the laboratory and thus provide
a model to validate the technique. For example, we can collect spectra from different positions in the cell (Fig. 1). We are currently applying this technique to urine samples collected from bladder Screen Shot 2014-07-31 at 2.33.00 PMcancer patients. We can distinguish normal urothelial cells from bladder cancer cells in these patients (Fig. 2). We are now collaborating with the Urologists at the Victoria Hospital, Kirkcaldy to see if this method can be used for following up patients to detect recurrence of their cancer.

 

 

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