Research Description
Moment-by-moment, the brain receives inputs about the state of the external environment and internal state of our bodies. For example, in between meals, it will monitor the levels of nutrients in the body, as well as availability of food around us. If nutrients within the body need replenishing, it will drive feeding and control the gut to ensure optimal food absorption. One of the main ways the brain commands the body and controls functions of the internal organs is through the vagus nerve. Interestingly, although the vagus nerve is comprised of thousands of individual cells, the textbook view so far has been that all of them are simultaneously active during feeding, eliciting a singular “rest and digest” response. However, recent work by the Liberles lab argues that the situation is much more complex, as these thousands of neurons do not all have an identical genetic structure, but form subtypes. Therefore, it is possible that subtypes of vagal neurons may be individually active based on the needs of the body, controlling only specific individual organs, or even just a specific function of that organ, such as the contraction of the stomach, or secretion of stomach acid. The work proposed here will test if this hypothesis is correct by recording and manipulating the activity of individual vagal neurons during hunger and feeding. These experiments will significantly further our understanding of how hunger originates and how digestion is controlled, and will prove an invaluable platform for developing new treatments for obesity and diabetes.Research Profile
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?The optimal maintenance of energy homeostasis, including food intake, digestion, and storage, requires a constant dialogue between the brain and peripheral tissues. The goal of my research is to bridge the fields of neuroscience and metabolism to understand how the brain controls our digestion and metabolism in health, and how this goes awry in diseases such as diabetes and obesity. With the technological advances at our disposal, we are now uniquely poised to dissect with unprecedented detail the neural circuits regulating our internal organs, allowing us to identify novel therapeutic approaches to treat, or even prevent, metabolic disorders.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?The vagus nerve connects the brain to essentially all major internal organs, including the gut and the pancreas. A recently discovered “parts list” of the vagus showed a striking diversity within the nerve, with multiple molecularly distinct cell types. It is exciting to consider that each of these neuronal subtypes may orchestrate distinct physiological control over digestion and metabolism. My project aims to understand the complex logic of how the brain precisely controls nutrient extraction from food and how it ensures proper utilization of this energy. The ultimate goal is to harness this knowledge to develop better, safer and long-lasting strategies for treating diabetes.
Why important for you, personally, to become involved in diabetes research? What role will this award play?Working as a clinician treating patients with diabetes and obesity, as well as through my own family members, I experienced the extraordinary daily burden of people living with those debilitating diseases. Despite decades of research, there is much we still do not understand on how metabolism is controlled and how and why diabetes develops. The American Diabetes Association Fellowship will allow me to become fully immersed in the global scene of cutting-edge diabetes research, and provide opportunities to learn from and collaborate with leading scientists in the field. I am confident that the training and knowledge I will receive during this fellowship will serve as the strongest foundation for my future independent scientific career. I hope that my research efforts will bring us closer to solving the current epidemic of metabolic disorders, and help improve the lives of people living with diabetes and obesity.
In what direction do you see the future of diabetes research going?There has been an increasing interest in understanding how the brain and the nervous system exert powerful coordinated control over multiple physiological processes, including metabolism. With the rate of ongoing technological and scientific advances, it is predicted that the next 50 years will lead to more discoveries in neuroscience than what has been produced during the entire history of humanity. I am thrilled to be conducting research in this era, where we can directly examine each of the millions of neurons within the brain at a single-cell resolution, and manipulate their activity to ascertain their exact functional role. Little by little, the brain will no longer be a mysterious black box, but an exquisitely rich discovery platform enabling the development of powerful approaches for diabetes treatment and prevention.