Pyruvate dehydrogenase E2 complex

Denis Burdakov Biography

Denis grew up in Kiev, benefiting from a Soviet school education that ranged evenly from mathematics to world literature. After moving to the UK in the 90s, he studied medicine and physiology at Oxford (Physiology Gibbs Prize, 2001). Continuing at Oxford as a Wellcome Prize student and Gustav Born scholar, he completed his DPhil under the supervision of Frances Ashcroft, investigating electrophysiological and molecular signatures of neurons in brain feeding centres. During his PhD, he became interested in sleep and wakefulness as well as metabolic regulation, and in 2004 was awarded a Royal Society Research Fellowship to study neurons that regulate both sleep and appetite. He held this fellowship at the University of Manchester (under the mentorship of Alex Verkhratsky), and then at Cambridge. Prior to joining NIMR he spent six years at the University of Cambridge, where he held a University Lectureship (tenured 2011) in the Department of Pharmacology, and was also a Fellow and Director of Studies in pharmacology and neuroscience at St. John’s College, Cambridge (2006-2012), and an affiliated investigator of the Institute of Metabolic Science. He moved his lab to NIMR in October 2012.

A key theme his recent work was sensing of the internal body state in the brain. These studies showed that glucose directly activates MCH-producing neurons (Burdakov et al, 2005), which drive sleep and energy conservation. This activation is now known to be crucial for peripheral glucose balance. Conversely, glucose stereo-selectively silences orexin/hypocretin-producing neurons (Gonzalez et al, 2008), which drive wakefulness and energy expenditure. Intrinsic adaptation allows the orexin cells to recover from unchangingly-high sugar levels, which makes their firing sensitive to glucose trends for a range of glucose baselines (Williams et al, 2008). The strength of glucose block of orexin cells depends on the physiological content of extracellular fluid: it is prevented by dietary amino acids (Karnani et al, 2011), energy fuels such as lactate (Venner et al, 2011), and acidification such as that caused by increased CO2 levels (Williams et al, 2007). Most recently, his lab showed that orexin neurons are able to signal to other cells not only through the slow-acting orexin peptides, but through rapid, millisecond-scale, glutamate signalling (Schone et al, 2012). Apart from experimental biology, he also has a long-standing interest in computational modelling of basic problems in cell physiology (Burdakov, 2005; Burdakov and Verkhratsky, 2006; Patel et al, 2012).

He received ERC-FP7 Starting Investigator award in 2008, and Human Frontiers Young Investigator award in 2012. His lab supported several PhD students and postdocs who went on to prestigious research fellowships and positions:

References

Burdakov group

Recent publications

Burdakov biography

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