Chairs
Professor Mike Murphy FMedSci, University of Cambridge
Dr Vsevolud Belousov, Russian Academy of Sciences, Russia
Professor Mike Murphy FMedSci, University of Cambridge
Mike Murphy received his BA in chemistry at Trinity College, Dublin in 1984 and his PhD in Biochemistry at Cambridge University in 1987. After stints in the USA, Zimbabwe, and Ireland he took up a faculty position in the Biochemistry Department at the University of Otago, Dunedin, New Zealand in 1992. In 2001 he moved to the MRC Mitochondrial Biology Unit in Cambridge, UK (then called the MRC Dunn Human Nutrition Unit) where he is a programme leader. Murphy's research focuses on the roles of reactive oxygen species in mitochondrial function and pathology. In particular he has pioneered the targeting of bioactive and probe molecules to mitochondria in vivo. Murphy is Professor of Mitochondrial Redox Biology at the University of Cambridge, a Wellcome Trust Investigator, honorary research Professor at the University of Otago, New Zealand, a recipient of the Keilin Medal from the Biochemical Society, an honorary Fellow of the Royal Society of New Zealand and a Fellow of the Academy of Medical Sciences (FMedSci).
Dr Vsevolud Belousov, Russian Academy of Sciences, Russia
Vsevolod Belousov received his Masters degree in biochemistry at Moscow State University, Russia in 1998 and PhD in Biochemistry at AN Belozersky Institute of Physical and Chemical Biology in 2002. After two years in Evrogen, where he was developing photoactivatable fluorescent proteins, he joined Segrey Lukyanov’s lab in the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry in Moscow to work on a genetically encoded H2O2 indicator. Since 2008 he has been a Redox biology group leader in the Institute of Bioorganic Chemistry. His interests are in genetically encoded redox probes development, super-resolution microscopy, optogenetics, metabolic engineering and anti-ischemic drugs development.
13:30-14:05
Use of fluorescent proteins as mitochondria redox probes
Dr Tobias Dick, German Cancer Research Center (DKFZ), Germany
Abstract
Hydrogen peroxide produced by mitochondria can act as a signaling molecule. It is increasingly realized that H2O2 signal transmission depends on thiol peroxidases which form redox relay chains with other proteins. The redox relay principle can be exploited to monitor endogenous H2O2 generation inside and outside mitochondria, in living cells and in real-time. These concepts and approaches now help to clarify which environmental, genetic or pharmacological perturbations impact on mitochondrial H2O2 emissions and signaling.
Show speakers
Dr Tobias Dick, German Cancer Research Center (DKFZ), Germany
Dr Tobias Dick, German Cancer Research Center (DKFZ), Germany
Tobias Dick graduated in biochemistry (FU Berlin) and obtained a PhD in molecular immunology with Hans-Georg Rammensee at the University of Tübingen. He was a Postdoctoral Fellow with Peter Cresswell at Yale University and then continued as an independent group leader in the field of Redox Biology at the German Cancer Research Center (DKFZ) in Heidelberg. In 2010, he was appointed Head of Division of Redox Biology at DKFZ. Dr Dick works on the molecular mechanisms of redox signalling and protein redox regulation. He develops tools for the visualisation and manipulation of redox processes in vivo. He uses these tools to investigate adaptive stress responses in normal and tumour cells.
14:05-14:40
Molecular imaging approaches to studying redox biology in the brain
Professor Christopher Chang, University of California, Berkeley, USA
Abstract
The exploration of the brain and its distinctive role in forming the centre of consciousness offers a grand challenge for achieving a molecular-level understanding of its unique functions, including learning and memory, as well as senses like sight, smell, and taste. As such, the brain also represents a frontier for developing new therapeutics for aging, stroke, and neurodegenerative diseases. We are developing molecular imaging approaches as a way to identify and study the underlying chemistry that governs brain activity. This talk will present our latest results in the discovery and understanding of reactive oxygen, sulphur, and carbon species as emerging new chemical signals and their influence on neural circuitry.
Show speakers
Professor Christopher Chang, University of California, Berkeley, USA
Professor Christopher Chang, University of California, Berkeley, USA
Christopher J. Chang is the Class of 1942 Chair Professor of Chemistry and Molecular and Cell Biology and HHMI Investigator at UC Berkeley, as well as a Faculty Scientist in the Chemical Sciences Division of Lawrence Berkeley National Laboratory. He was born in Ames, IA and received his B.S. and M.S. degrees from Caltech in 1997, working with Professor Harry Gray. After spending a year as a Fulbright scholar in Strasbourg, France with Dr Jean-Pierre Sauvage, Chris received his PhD from MIT in 2002 under the supervision of Professor Dan Nocera. He stayed at MIT as a postdoctoral fellow with Professor Steve Lippard and then began his independent career at UC Berkeley in 2004. Research in the Chang lab is focused on chemical biology and inorganic chemistry, with particular interests in molecular imaging and catalysis applied to neuroscience, metabolic and infectious diseases, and sustainable energy. His group's research has been honoured by awards from the Dreyfus, Beckman, Sloan, and Packard Foundations, Amgen, AstraZeneca, and Novartis, AFAR, Technology Review, ACS (Cope Scholar, Eli Lilly Award in Biological Chemistry), RSC (Transition Metal Chemistry), and the Society for Biological Inorganic Chemistry, and in 2013 Chris was awarded the Noyce Prize at UC Berkeley for excellence in Undergraduate Teaching. Most recently Chris received the 2013 ACS Nobel Laureate Signature Award in Graduate Education, 2013 Baekeland Prize, and 2015 Blavatnik Laureate in Chemistry. He is a Senior Editor at ACS Central Science.
15:30-16:00
Chemical biology of H2S signaling: the role of mitochondria
Dr Milos Filopovic, University of Bordeaux, IBGC UMR 5095 and CNRS, IBGC, UMR 5095, France
Abstract
Hydrogen sulphide (H2S) is a gasotransmitter involved in the regulation of blood pressure and synaptic plasticity. More importantly H2S has a strong therapeutic potential in treating ischemia-reperfusion injury. The mechanisms behind many (patho)physiological roles assigned to H2S are, however, still elusive. The cross-talk of H2S with NO (and its metabolites) started emerging as a mechanistic concept that can explain some of the physiological effects assigned to H2S. Several new signalling molecules have been identified as products of the above-mentioned cross-talk. Endogenous H2S generation seems to be important for the process of tran-S-nitrosation in the cells, presumably through the formation of thionitrous acid (HSNO). Mitochondrial hem centres play particular role in HSNO generation. Furthermore, H2S reacts directly with NO to generate nitroxyl (HNO), which then activates the TRPA1 channel to allow Ca2+ influx into sensory nerve endings. This stimulates the release of the strongest known vasodilator, calcitonin gene-related peptide. On the other hand, protein persulfidation, an oxidative posttranslational modification of cysteine residues, is also believed to be responsible for most of biological effects controlled by H2S. Majority of protein persulfidation is located in mitochondria and mercaptopyruvate sulfur transferase, an H2S producing enzyme predominantly located in mitochondria, plays important role in this process. Furthermore, in order to be regulatory, protein persulfidation would have to be tightly regulated, i.e. the mechanism for protein de-persulfidation would have to exist. We discovered recently that thioredoxin system acts as depersulfidase, controlling thus the H2S signaling. The role of mitochondria in this process will be additionally discussed.
Show speakers
Dr Milos Filopovic, University of Bordeaux, IBGC UMR 5095 and CNRS, IBGC, UMR 5095, France
Dr Milos Filopovic, University of Bordeaux, IBGC UMR 5095 and CNRS, IBGC, UMR 5095, France
-
Dr Milos Filopovic, University of Bordeaux, IBGC UMR 5095 and CNRS, IBGC, UMR 5095, France
-
Dr Milos Filopovic, University of Bordeaux, IBGC UMR 5095 and CNRS, IBGC, UMR 5095, France
- Membership status unknown
- No primary institution
Milos R. Filipovic graduated biochemistry from the University of Belgrade, Serbia, where he also obtained his PhD in 2008. After a short visit to L’Ecole Normal Supérieure in Paris, as a FEBS fellow, Milos joined the Bioinorganic Chemistry Division at Friedrich-Alexander University Erlangen-Nuremberg, first as a postdoc, and then as an independent group leader/habilitant. In 2015 he received ATIP-Avenir and Idex Junior Chair grants, and was subsequently appointed as a group leader at CNRS, Institute of Cellular Biochemistry and Genetics UMR5095, at the University of Bordeaux. His research is focused on biochemical mechanisms behind the intracellular signalling by gasotransmitters (nitric oxide and hydrogen sulphide), on their cross-talk and on post-translational modifications of proteins caused by these gaseous molecules. Most recently he has become particularly interested in signalling by H2S in mitochondria.
16:00-16:35
Nitric oxide and mitochondria
Sir Salvador Moncada FRS, University College London
Abstract
Nitric Oxide (NO) inhibits mitochondrial cytochrome c oxidase (Complex IV) in a reversible manner and at physiological concentrations. Its affinity for NO is greater than that for oxygen (O2) suggesting that NO might regulate O2 consumption or interfere with its usage in pathological situations. For review see, [1]. We discovered that long-term inhibition of Complex IV led to persistent inhibition of complex I, a process which is dependent on free radical generation most probably from the mitochondria.[2]. Inhibition of Complex I is dependent on the nitrosation of a critical cysteine which is exposed during the conformational change of the enzyme from its active to its deactive form in hypoxia (A/D transition) [3]. This locks Complex I in its nitrosated state arresting its activation and affecting cellular energy production. We speculated, that hypoxic deactivation may act as a protective intrinsic mechanism against ischemia/reperfusion injury, but at the same time could initiate mitochondria-dependent pathophysiology during oxidative or nitrosative stress [3, Nitric Oxide (NO) inhibits mitochondrial cytochrome c oxidase (Complex IV) in a reversible manner and at physiological concentrations. Its affinity for NO is greater than that for oxygen (O2) suggesting that NO might regulate O2 consumption or interfere with its usage in pathological situations. For review see, [1]. We discovered that long-term inhibition of Complex IV led to persistent inhibition of complex I, a process which is dependent on free radical generation most probably from the mitochondria.[2]. Inhibition of Complex I is dependent on the nitrosation of a critical cysteine which is exposed during the conformational change of the enzyme from its active to its deactive form in hypoxia (A/D transition) [3]. This locks Complex I in its nitrosated state arresting its activation and affecting cellular energy production. We speculated, that hypoxic deactivation may act as a protective intrinsic mechanism against ischemia/reperfusion injury, but at the same time could initiate mitochondria-dependent pathophysiology during oxidative or nitrosative stress [3, 4]
1. Moncada, S. and J.D. Erusalimsky, Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nat Rev Mol Cell Biol, 2002. 3(3): p. 214-20.
2. Clementi, E., et al., Persistent inhibition of cell respiration by nitric oxide: crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione. Proc Natl Acad Sci U S A, 1998. 95(13): p. 7631-6.
3. Galkin, A. and S. Moncada, S-nitrosation of mitochondrial complex I depends on its structural conformation. J Biol Chem, 2007. 282(52): p. 37448-53.
4. Galkin, A., et al., Lack of oxygen deactivates mitochondrial complex I: implications for ischemic injury? J Biol Chem, 2009. 284(52): p. 36055-61.
Show speakers
Sir Salvador Moncada FRS, University College London
Sir Salvador Moncada FRS, University College London
"Salvador Moncada, MD, obtained his PhD in 1973 at the Royal College of Surgeons in London. He then moved to the Wellcome Research Laboratories where he initiated the work leading to the discovery of the enzyme thromboxane synthase and the vasodilator prostacyclin. He was also responsible for the identification of nitric oxide as a biological mediator and the elucidation of the metabolic pathway leading to its synthesis. Since 1996 Professor Moncada has directed the Wolfson Institute for Biomedical Research at University College London. He continued his research in the areas of mitochondrial biology and cell metabolism where he made significant contributions. His current research is concentrated in the area of cell proliferation. Professor Moncada is a Fellow of the Royal Society and a Foreign Associate of the National Academy of Science of the USA and in 2010 he received a Knighthood for his services to Science."