Projects involving members of the Health Science Research Centre
Going on holiday, having a fun night out with friends, or simply relaxing at home with a good book – these activities make us feel good - mentally but also physically. How’s this working? Is it really just ‘resting’ or ‘relaxing’? And even if so, how do resting, relaxing, ‘being happy’ make our body function better?
Professor Fulvio D’Aquisto’s area of research is called ‘Affective Immunology’ (www.affectiveimmunology.com) and its aim is to discover what are the genes, molecules and cells of the immune systems that respond to changes in lifestyle and living conditions.
We plan to use this information to answer some basic but yet fundamental scientific questions:
- How does our body or immune system react to good or bad living conditions?
- Can changes in lifestyle be used as a way to improve the ability of humans to clear infections and heal from inflammatory/immune diseases?
- Is the understanding and appreciation of one's living conditions important for the design of 'tailor-made' treatments for infectious and inflammatory disorders?
We hope that answering these questions will help us make people appreciate how important are social interactions and good living conditions for the immune system. Indeed, now more than ever the cure for a disease and the secret of a good living is not just in a pill!
Research on novel psychoactive substances (NPS) and their addictive properties
Novel psychoactive substances (NPS), formerly known as 'Legal highs' are increasingly prevalent in Europe and elsewhere although their pharmacological characteristics are largely unknown. NPS with stimulant properties have addictive potential which their users might not realise. Stimulants act at the dopamine transporter (DAT) and subsequently increase dopamine concentrations in the brain, including its reward and addiction pathways.
In the present programme of research led by Professor Jolanta Opacka-Juffry, we use both neurobiological and molecular modelling methods to characterise the stimulant properties of NPS. The molecular modelling studies conducted by means of high performance computing (HPC) by Dr Michelle Sahai, an expert in computational biomedicine at Roehampton, reveal the molecular details and patterns of NPS binding with brain targets such as DAT. They also demonstrate the benefits of combining computational methods of biophysics with experimental neurobiological procedures to determine structural and functional properties of NPS at their molecular targets in the brain. This research is of relevance to the society: NPS users, addiction support and health services as well as policy makers.
The present research is taking place in collaboration with Professor Colin Davidson of the University of Central Lancashire as well as the Blenheim Charity, London www.blenheimcdp.org.uk.
Research on the bone marrow microenvironment in acute myeloid leukaemia (AML) – Cancer Research UK grant
Acute Myeloid Leukaemia (AML) results from the accumulation of malignant myeloid blasts in the bone marrow (BM) due to abnormal proliferation and differentiation of haematopoietic progenitor cells. Although current therapies induce high rates of remission there is still an unmet need for new therapeutic strategies as the majority of patients with AML tend to relapse. There is emerging evidence of a crucial role of adhesive interactions between AML leukemic stem cells and the BM normal cells during AML development and resistance to drug treatment.
This CRUK-funded project led by Dr Yolanda Calle-Patino aims to develop a new cell culture method to identify drug combinations that target AML cells and the supportive BM normal cells that could overcome cell adhesion-mediated drug resistance to drugs commonly used against AML, and be progressed as new and more effective therapies against AML. Thus this research is of significance to both drug discovery and basic research studies to identify signalling pathways that regulate AML biology. Dr Yolanda Calle-Patino leads her team at Roehampton with Dr Yoana Arroyo (post-doctoral research fellow) and Mariacristina Ciccioli (research student), and collaborates with Professors Lucy Di Sylvio and Eric So of King’s College London, as well as Drs Laurent Lacroix and Volker Behrends (HSRC).
Understanding the role of phosphatase PP2A on chemotherapy resistance of Mixed Lineage Leukaemia (MLL) – Leuka Foundation grant
This project, led by Dr Maria Theresa Esposito is focused on Mixed Lineage Leukaemia (MLL), an aggressive form of acute leukaemia mostly affecting paediatric patients. The treatment is based on chemotherapy followed by bone marrow transplantation, however, because of the development of drug resistance, the prognosis is dismal with survival ranging from 20 to 50%.
Molecular approaches have dramatically improved our understanding of this disease. Several survival pathways are activated in MLL leukemic cells. The activity of these pathways mostly depends on the balance between phosphorylation reactions, which are mediated by kinases and activate the survival pathways, and de-phosphorylation which are mediated by phosphatases and inhibit the survival pathway.
PP2A is a phosphatase and a tumour suppressor found inactivated in several forms of cancer. Notably, PP2A Activating Drugs (PADs) have shown therapeutic efficacy in leukaemias and solid tumours. Our preliminary data indicate that PP2A is inactivated in MLL cell models. The objectives of our study are to investigate the mechanisms by which PP2A inactivation occurs in MLL and investigate the effect of PP2A reactivation on MLL’s response to chemotherapy. Our aim is to design new targeted therapeutic strategies for MLL patients who currently lack life-saving treatment options.
Research on diabetes: Cell-cell communication and the regulation of islet function - Diabetes UK funding
Diabetes is one of the most well-known and rapidly expanding chronic metabolic conditions, affecting more than 3.5 million people in the UK today. The present project led by Dr Astrid Hauge-Evans is focussed on the regulation of insulin production from the beta cell within the pancreatic islet, since beta cell dysfunction is one of the main underlying causes of the disease.
The islets are small, spherical organs scattered throughout the pancreas and this research project investigates how different cell types within these structures communicate with each other and modulate the functional capacity of the islets both with regard to hormone release and beta cell survival. Defining the mechanisms and consequences of intra-islet cell-cell communication is important for identifying novel therapeutic targets for Type 2 diabetes and for designing effective graft material for transplantation therapy of Type 1 diabetes.
The research is led by Dr Astrid Hauge-Evans with her team in collaboration with Professor Peter Jones, Diabetes Research Group, King’s College London.
Can stress lead to obesity or metabolic disease? Science without Borders PhD grant
Stress affects us all in different ways; however a significant group of people overeat when they are stressed and this can lead to obesity and metabolic disease. In 2015 University of Roehampton was awarded a prestigious scholarship (2016-18) from the Brazilian Government’s Science Without Borders - Ciência sem Fronteiras scheme to allow Simone Carneiro Nascimento to perform ground breaking research in this area under the expert supervision of Professor Jolanta Opacka-Juffry Dr Michael Patterson (HSRC, Roehampton) and Professor Chris Pryce (University of Zurich). This international collaboration has yielded some exciting results. Simone has found that social stress alters both the hormonal systems that regulate body weight, and the neurochemical signals in our brain that signal reward after food and other pleasurable experiences. Simone has presented these results to experts from around the world at two leading Neuroscience conferences. She is now working hard to expand on these findings and we hope her research will lead to a better understanding of how to treat stress related overeating.
Gluten Friendly Study on the effects of gluten friendly bread in coeliac disease patients
In the last two decades, there has been an increase in Coeliac Disease (CD), a life-long intolerance to gluten proteins present in most cereals, across Europe, the United States and developing countries. Recently, a new and innovative gluten detoxification method has been developed. This technology induces structural modifications of gluten without compromising the nutritional and technological properties necessary to process flour into bread, pasta and other baked goods. The gluten is still present in the modified bread but it becomes unrecognizable by antibodies. As such the modified bread is referred to as “Gluten Friendly” and not “Gluten-free”.
Dr Adele Costabile leads this project at Roehampton, to investigate the effects of the Gluten Friendly bread on coeliac disease patients. The study will assess the effects on the intestinal permeability, inflammation, immunity and microbiota composition. High-Performance Computing techniques are used to better understand how the 3-dimensional structures of the gluten proteins at the molecular level affect their functional characteristics. So far the in vitro results are encouraging and this project could have a high impact on society through decreasing the incidence of coeliac disease. This project is funded by the University of Foggia, Italy.
Toy Box Malaysia – MRC grant - an international collaboration
Globally, obesity is increasing at an alarming rate. According to the World Health Organisation in South East Asia 350 000 deaths are attributed to overweight and obesity annually and the country with the highest incidence is Malaysia. Amongst children it is estimated that 23% of boys and 19% of girls are overweight or obese which has led the Malaysian Association for the Study of Obesity to conclude that strategies and interventions to prevent childhood obesity are urgently required.
The Toy Box study is a large scale obesity intervention aimed at pre-school children that to date has been implemented in six European countries. The intervention is based in pre-school and kindergarten facilities and is centred around four energy balance related behaviours; encouraging water consumption, eating healthy snacks, reducing sedentary behaviour and increasing physical activity.
The aim of this Medical Research Council funded research is to conduct a feasibility study into the use of the Toy Box intervention in rural and urban settings in Peninsular Malaysia and Sarawak.
Grant holders at Roehampton: Dr Sue Reeves (HSRC), Dr Leigh Gibson (PI) and Prof Cecilia Essau, both Department of Psychology, University of Roehampton.