Contribution of Tanycytes to the control of bodyweight, food seeking and intake

Programme overview:
This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.

Project:
The balance of key bodily functions such as temperature, food intake and energy expenditure is governed by an area of the brain known as the hypothalamus. In terms of feeding, cells within the hypothalamus can detect nutrients from food which have made their way into the blood. Multiple nutrient-detecting cells have been identified, including non-neuronal cells within the hypothalamus, named tanycytes. These tanycytes respond to both glucose and amino acids. Interestingly, amino acids are known to supress hunger more than any other nutrient. As amino acids are detected by tanycytes and are known to reduce hunger, this study aims to fill the missing link between tanycytes and feeding behaviour.

Using new, miniaturised microscopes which can visualise the brains of conscious mice, this study will analyse real-time tanycyte activity. This will allow us to determine the effect meals have on tanycyte behaviour and the effect tanycytes have on feeding (by artificially enhancing or reducing tanycyte activity). After developing the required in vivo skills, tanycytes will be monitored in freely behaving mice and specific aspects of mouse diets will be varied. This includes the level of amino acids in meals or the restriction of meals for short periods of time, to see the impact it has on tanycytes. All data regarding tanycyte activity and feeding will then be linked to changes in weight.

The real-time images of tanycytes will be enhanced to increase resolution using computational methods such as deconvolution. To achieve this, each lens used will be characterised, incorporating mathematics and physics, to improve image quality. Using computer science, an algorithm to detect tanycytes can also be developed, much like current programs which automatically detect neurons. This will make the analysis of tanycyte data less time intensive. With knowledge of the role tanycytes play in the control of bodyweight, we can create informed strategies to improve societal health.