The Role of Non-Coding RNA for Body Weight Regulation

Background: The prevalence of obesity in the United Kingdom continues to rise. The main causes of obesity are behavioural: increased feeding behaviour and decreased physical activity. Recent studies that employed transcriptomic analyses of brain regions implicated in body weight regulation have identified several novel RNA; these RNA are strong candidate markers of obesity and suggest a potential role for the neural regulation of food intake and body weight. The aim of this studentship is to examine the mechanisms that govern the expression of these novel RNAs and develop approaches that gain control over body weight. Projects will include environmental and diet induced changes in RNA expression, nutritional physiology and feeding behaviour. The overall goals are to identify novel targets for the treatment and reduction of obesity.

The PI’s laboratory studies daily and seasonal rhythms in the Siberian hamster. Hamsters are a model seasonal species due to their marked physiological, behavioural and immune responses to simple changes in day length (15hrs to 9hrs light). Recent evidence from the PIs laboratory has revealed short days induced changes in hypothalamic non-coding RNA (ncRNA) in brain regions involved in body weight regulation. ncRNA are critical regulators of gene expression; therefore provide the opportunity to identify new targets for body weight regulation. The objectives of this proposal are to uncover the mechanisms that regulate light induced changes in ncRNA and then place variation in ncRNA into a functional context.

Approach: This project will require a multi-disciplinary and integrative project that will take advantage of the strong biological rhythms groups in the Institute of Biological and Environmental Sciences (IBES) and Rowett Institute of Nutrition and Health (RINH). It is expected that this PhD studentship will require a series of interconnected investigations.

Training: This studentship will be involved in light and diet induced changes in hamster body weight. Students will receive hands-on training in expert animal care and husbandry. Methodological approaches may include several molecular biology techniques such as RNA extraction, qPCR, in situ hybridization, immunohistochemistry and hormonal measurements. Establishing functional roles of targeted genes is another goal of the laboratory research interests. To address this, we use intracerebral injections that inhibit or enhance target RNA expression. Students are encouraged to develop other in vivo or in silico approaches to examine the relationship between neuroendocrine and behavioural plasticity. This studentship will expose the student to broad fields of research including: neuroanatomy, neuroscience, physiology, and animal behaviour. The student will take the lead role in data collection, interpretation and drafting manuscripts. PI maintains an open-door policy for trainees and will welcome requests for assistance at each step. Students will also be encouraged to engage other scientists in the respective institutes to foster their own collaborations. Lastly, the student will attend and present their findings at several UK meetings as well as international conferences.