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Professor Yves Barde FRS

Professor Yves Barde

FRS

Emeritus Professor

Email
bardey@cardiff.ac.uk
Comment
Media commentator

Overview

Our work focuses on growth factors known to play key roles in brain development and function. Some of these growth factors are found not only in the brain, but also in circulating blood platelets and we are exploring the possibility that they may be delivered to the nervous system by small vesicles derived from platelets. To this end we have generated a new mouse model allowing this hypothesis to be tested. This approach takes advantage of a major difference between mouse and primates with regard to the growth factor content of platelets. Specifically, platelets of primates contains very significant amounts of brain-deriived neurotrophic factor (BDNF), whilst BDNF is undetectable in mouse platelets. Mice were then engineered to express BDNF in megakaryocytes, with the result that their platelets contain BDNF levels comparable to humans. This work could lead to novel ways of delivering genetically encoded macromolecules to the brain over long periods of time and the potential of this approach is being explored with our colleagues at the School of Optometry. We also use extensively human neurons derived from embryonic stem cells to explore poorly understood aspects of neurotrophin signalling, including the interactions of BDNF and Neurotrophin-3 with their cognate receptors.

Biography

Medical School & Doctor of Medicine (Geneva, 1975)

Swiss Certificate of Molecular Biology (Basel, 1977)

Postdoctoral fellow, Department of Pharmacology (Basel, 1976)

Postdoctoral fellow, Max-Planck Institute of Psychiatry (Martinsried, Germany, 1979)

Schilling Professorship, Max-Planck Institute of Psychiatry (Martinsried, Germany, 1989)

Scientific member of the Max-Planck Society, Director, Max-Planck Institute of Neurobiology (Martinsried, Germany, 1991)

Honorary Professor of Neurobiology, Ludwig Maximilian University (Munich, Germany, 1993)

Director of the Friedrich Miescher Institute for Biomedical Research (Basel, 2001)

Professor of Neurobiology Phil II Faculty (Basel, 2001)

External Scientific Member of the Max-Planck Institute of Neurobiology (Martinsried, 2002)

Professor of Neurobiology, Division of Pharmacology and Neurobiology (Basel, 2003).

Sêr Cymru Research Chair in Neurobiology (Cardiff University, 2013)

Fellow of the Royal Society (London, 2017)

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Much has been learned about molecular mechanisms operating in the mammalian nervous system using genetically modified animals. In particular, the relevance of growth factors initially identified on the basis of cell culture assays could be firmly established by selectively eliminating the corresponding genes, typically using the mouse as model organism. These experiments have greatly helped understanding the physiology of brain-derived neurotrophic factor (BDNF) and of its tyrosine kinase receptor TrkB. BDNF is a secreted protein initially identified on the basis of its ability to promote the survival of specific populations of sensory neurons (https://www.embopress.org/doi/abs/10.1002/j.1460-2075.1982.tb01207.x). Most of the current work now focusses on the role of BDNF in synaptic plasticity, a key aspect of memory-related mechanisms, as well as in neuroprotection in humans. Whilst the generation of mouse mutants has been a key driver thus far, it is also evident that there are major differences between primates and rodents. These include the distribution of BDNF and the sites of its biosynthesis. In particular, circulating blood platelets contain significant levels of BDNF in humans, higher than in the brain (https://www.eneuro.org/content/5/2/ENEURO.0419-17.2018). But such is not the case in the mouse, with the implication that the hypothesis that blood-derived BDNF may impact brain function could not be tested thus far. This is as such an interesting question given that the levels of BDNF increase in human serum after physical exercise and that the benefits of exercise towards maintaining or improving important aspects of brain function are well appreciated.

Our recent work led to the identification of megakaryocytes as the cellular origin of BDNF in human platelets (http://www.jbc.org/content/291/19/9872). Based on the related observation that mouse megakaryocytes do not contain BDNF, we recently generated a mouse model mimicking the situation in primates. In collaboration with colleagues at Cardiff University we are testing the possible benefits of blood-derived BDNF using this mouse model.

Work in our laboratory also involves the extensive use of neurons derived from embryonic stem cells to test novel reagents activating the BDNF receptor TrkB and the Neurotrophin-3 receptor TrkC after eliminating TrkB in human embronic stem cells. This work involves collaborations with the biotechnology industry giving us access to novel antibodies able to activate TrkB and other receptors of interest (see https://www.pnas.org/content/115/30/E7023).

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