Investigating BACE1 as a novel regulator of adipose thermogenesis and cardiometabolic disease
Supervised by: Dr Amanda MacCannell, Faculty of Medicine and Health, University of Leeds
Project Background
Over 64% of adults in England are obese or overweight, costing the NHS £6.1 billion a year. Carrying excess weight is a direct driver of serious illness, including heart disease and the primary cause of dyslipidemia (excess lipid in other tissues), insulin resistance, hypertension and atherosclerosis (plaques in blood vessels). We used to think that fat simply as the body’s way of storing spare energy, but we now know it is far more active than that. Fat sends signals to other organs, helps control how the body uses energy and comes in different varieties for different jobs. Most familiar is white fat, which stores excess calories. Less well known is “brown fat,” which actively burns excess lipids to produce heat and improve metabolic health. If we could reliable activate brown fat, the body could burn off excess fat from the blood and tissues, offering a powerful new way to tackle obesity and its consequences. A drug developed to treat Alzheimer's disease, targeting a key protein involved in the brain plaques that drive the condition, produced a striking side effect in clinical trials: significant weight loss. This suggested the protein it targets might also play an important role in how the body manages fat.
That protein is an enzyme called BACE1. This project investigates whether BACE1 acts as a brake on the body's ability to burn fat. Early evidence suggests it does, that BACE1 promotes fat storage and prevents fat tissue from switching into its energy-burning mode. If so, blocking BACE1 could release that brake, encouraging fat tissue to burn rather than store excess lipids, and offering a genuinely novel approach to treating obesity, heart disease, and metabolic conditions.
Research Question
How does blocking or removing BACE1 affect fat cell metabolism and thermogenesis?
Objectives
Working under the supervision of Dr Amanda MacCannell I will gain experience studying how fat tissue functions at the molecular and cellular level. I will work with fat tissue from mice in which the BACE1 gene has been specifically removed from adipose tissue, alongside control samples. Furthermore, I will utilise laboratory techniques to assess changes in fat structure, gene activity, and protein levels linked to energy burning and lipid storage. This includes staining tissue sections to visualise fat cells, measuring gene expression using qPCR, and analysing proteins by Western blotting. Throughout this 6-week research project I will expand upon my knowledge of experimental design, data collection and analysis, and how these results help answer important biological questions about metabolism and cardiovascular Health. The project will provide insight into how laboratory research contributes to understanding disease mechanisms and developing future treatments for obesity and related cardiometabolic disorders. The outcomes of this research will be measured through changes in molecular and tissue markers linked to fat cell thermogenesis and lipid metabolism
Impact
This research will contribute new insights into the role of fat tissue BACE1 in regulating metabolism, obesity, and obesity-induced cardiovascular disease. The findings will contribute directly into the evidence base of the British Heart Foundation–funded research programme “Adipose tissue BACE1 as a therapeutic target for obesity and obesity-induced atherosclerosis”, supporting its scientific deliverables and long-term translational impact.
Motivation
As a neuroscience undergraduate student, I first encountered BACE1 in the context of Alzheimer's disease, where is plays a central role in the formation of brain plaques that drive the condition. When I discovered that the same protein might also play a role in multiple different biomedical areas, I was struck by how a single protein could sit at the intersection of such different disease. Since starting my degree there has been a large focus on viewing the body as an interconnected system not individual systems working in isolation. I believe this project is an opportunity to see this in practice alongside contributing to research that could impact disease management.
Opportunities for collaboration
I welcome any further questions about this research project. I want to make the most of this research opportunity and my time on the Laidlaw programme as a whole, I would really appreciate any additional insight into this area of research from professionals or other Laidlaw undergraduate researchers investigating related areas of biomedical research. Please feel free to Contact me on the Laidlaw Scholars Network, or on LinkedIn.