Mitochondrial physiology, redox biology, and genetics
What can you expect from MitoPorto 2023?
In this fourth edition of MitoPorto we highlight mitochondrial physiology, redox biology, and genetics. We also welcome communications from scientists with a multidisciplinary interest in mitochondrial research (e.g. in the context of neuroscience, cancer, metabolism). The program will combine keynote lectures with oral communications selected from the abstracts. Poster sessions will allow participants to discuss their work with fellow scientists and extend collaborative networks. After a productive scientific meeting in Porto, why not extend your stay in this European Top Destination, the World´s Leading City Destination of 2022.
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. This general methodology is now widely used. Prominent mitochondria-targeted compounds are antioxidants, such as MitoQ, which protects against oxidative damage in ischaemia-reperfusion injury. Murphy and Rob Smith developed MitoQ as an oral drug which has been used in two Phase II trials so far. This work established mitochondria as a relevant drug target and opened up the field of mitochondrial pharmacology. The Murphy group has gone on to create MitoSNO, a mitochondria-targeted nitric oxide donor which is now being developed as a potential therapy for cardiac ischaemia-reperfusion injury, and MitoG to treat diabetes. Recently his work has extended to determining the mechanism by which mitochondria produce free radicals during ischaemia-reperfusion injury in heart attack and stroke. Murphy is Professor of Mitochondrial Redox Biology at the University of Cambridge, a Wellcome Trust Investigator, an MRC Investigator, an 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). He has published more than 420 peer reviewed papers, which have garnered more than 63,000 citations and he has an h-index of 129.
Laura Greaves is a Principle Investigator and Senior Lecturer in the Wellcome Centre for Mitochondrial Research at Newcastle University where she leads the Stem Cell and Cancer Metabolism Laboratory. She obtained her PhD at Newcastle University studying the role of mitochondrial DNA mutations in colorectal stem cell ageing in 2005 before completing her post-doctoral studies utilising mitochondrial DNA mutations as lineage tracing marks in stem cell populations. She established her own laboratory in 2016 where her team is now focussed on understanding the role of age-associated mitochondrial dysfunction in intestinal stem cell biology and tumorigenesis. The lab uses a wide range of state-of-the-art experimental approaches, ranging from multi-omic analyses of genetically modified mouse models and organoids to multiplex immunofluorescent analyses of mitochondrial function in large human colorectal cancer cohorts. Outside of work Laura is a keen runner and cyclist who lives with her partner Barry and their five year old son Toby.
Pedro Silva-Pinheiro is a Research Associate at the MRC Mitochondrial Biology Unit in Cambridge, UK. He received his BS in Genetics and Biotechnology from the University of Trás-os-Montes and Alto Douro and a MSc in Molecular Medicine from the University of Porto, Portugal. During his MSc, Silva-Pinheiro was awarded a Fulbright Scholarship allowing to carry his research at the University of Alabama in Birmingham, US, studying the effects of mitochondrial DNA mutations in lipid metabolism. Then, he joined the group of Massimo Zeviani in the MRC Mitochondrial Biology Unit, University of Cambridge supported by a Marie Skłodowska-Curie PhD studentship. During his PhD, Silva-Pinheiro focused on the pathogenesis and development of therapies for mitochondrial diseases using mouse models. Silva-Pinheiro has now joined the group of Michal Minczuk in the MRC Mitochondrial Biology Unit where he focuses on mitochondrial DNA editing techniques.
Pedro Silva-Pinheiro current research interests lie on the development and application of new methods for manipulation of mammalian mitochondrial DNA (TALE nucleases and base editors - DdCBEs), allowing for the generation of new models of mitochondrial disease and novel therapeutic platforms.
Recent publications include: “Silva-Pinheiro, P., Mutti, C.D., Van Haute, L. et al. A library of base editors for the precise ablation of all protein-coding genes in the mouse mitochondrial genome. Nat. Biomed. Eng (2022). https://doi.org/10.1038/s41551-022-00968-1” and “Silva-Pinheiro, P., Nash, P.A., Van Haute, L. et al. In vivo mitochondrial base editing via adeno-associated viral delivery to mouse post-mitotic tissue. Nat Commun 13, 750 (2022). https://doi.org/10.1038/s41467-022-28358-w”.
Ayesha Sen is a PhD student at the University of Cologne, in the Centre for Physiology and Pathophysiology. She grew up in Darjeeling, India and received her Bachelors degree in Biotechnology from Amity University, Uttar Pradesh. During her Bachelor’s she studied the role of Notch signalling in Planaria regeneration, and tissue reorganization in Hydra Magnipapillata, at the Institute for Stem Cell Biology and Regenerative Medicine (InStem), Bengaluru, working under the supervision of Dr. Dasaradhi Palakodeti. She moved to Germany for her higher education, and did a Master’s in Molecular Biology and Biotechnology from the University of Bonn. For her Master’s thesis, she joined the group of Prof. Dr. Rudolf Wiesner at the University of Cologne, where she studied the link between mitochondrial dysfunction and inflammation in keratinocytes, supported by a fellowship by the SFB 829 (Molecular Mechanisms regarding Skin Homeostasis).
Her current research interests are to investigate the maintenance of mtDNA integrity, specifically in muscle satellite cells, in the context of ageing and sarcopenia. She is studying this under the supervision of Dr. David Pla-Martín and Prof. Dr. Rudolf J. Wiesner.
Her recent publications include “Kimoloi S, Sen A, … Wiesner RJ, Pla-Martín D, Baris OR. Combined fibre atrophy and decreased muscle regeneration capacity driven by mitochondrial DNA alterations underlie the development of sarcopenia. J Cachexia Sarcopenia Muscle (2022). https://doi.org/10.1002/jcsm.13026”, “Sen A, … Wiesner RJ, Pla-Martín D. Mitochondrial membrane proteins and VPS35 orchestrate selective removal of mtDNA. Nat Commun (2022). https://doi.org/10.1038/s41467-022-34205-9” and “Sen A, Boix J, Pla-Martín D. Endosomal-dependent mitophagy coordinates mitochondrial nucleoid and mtDNA elimination. Autophagy (2023). https://doi.org/10.1080/15548627.2023.2170959 ”
Mitochondrial diseases encompass a complex genetic landscape, with 99% protein gene-products encoded by the nuclear genome. Yet the tiny mitochondrial DNA itself encodes genes vital to life and mitochondrial biogenesis and accounts for ¾ of all mitochondrial-disease mutations. These diseases show a surprisingly diverse array of variable physical manifestations, age of onset, and severity in patients – even for mutations within the same gene. This tissue and cell-specific variability in the disease presentation necessitates animal model research to understand these phenomena and lead to translational breakthroughs for mitochondrial disease patients. Despite advances in nuclear genome-engineering, animal mitochondrial-DNA has remained resistant to transgenic manipulation. Our team is among only three labs in the world who have generated these pathogenic mitochondrial-DNA mouse models. Work continues on charactering the pathophysiology of these models, and on pre-clinical experimental therapies for these disorders. We are also interested in mouse models where nuclear gene mutations alter mitochondrial DNA mutagenesis or lead to structural mutations in the mitochondrial chromosome.
Vanessa A. Morais obtained her PhD degree from ITQB/FCT-UNL, Lisbon - Portugal. Her PhD involved a long-term stay as a visiting scholar at the CNDR at UPENN, Philadelphia, USA, in the laboratory of Prof. Dr. Virginia M.-Y. Lee. After her PhD, Vanessa went on with her postdoctoral studies at VIB, Leuven, Belgium, in the laboratory of Prof. Dr. Bart de Strooper; with a long-term stay at VIMM, Padua, Italy, in the laboratory of Prof. Dr. Luca Scorrano. In 2009, Vanessa became a Staff Scientist at VIB and an Associate Professor at KULeuven, Belgium. In 2015, Vanessa returned to Portugal as a Group Leader at iMM – Instituto de Medicina Molecular, Lisbon; and is also an associate professor at Faculty of Medicine University of Lisbon. Vanessa is head of Mitochondrial Biology and Neurodegeneration laboratory and her research is focused on mitochondrial biology and neurodegeneration.
Our overarching goal is to clarify the intimate crosstalk between the host cell – the neuron – and the powerhouse organelle – the mitochondria. Mitochondria at the synapse have a pivotal role in neurotransmitter release, but almost nothing is known about synaptic mitochondria composition or specific functions. Synaptic mitochondria compared to mitochondria in other cells, need to cope with increased calcium load, more oxidative stress, and high energy demands that sustain neurotransmitter release and synaptic plasticity. Our research interests aim at deciphering the intrinsic properties of synaptic mitochondria and to scrutinize their relevance for the healthy brain. For this, we aim to assess the protein fingerprint, the metabolic profile and fuel preference of synaptic mitochondria; the mitochondrial clearance and biogenesis rates at synapse, as well as the contribution of mitochondrial dynamics to neural stem cell fate. Ultimately, we intend to unveil how disruption of these synapse-specific mechanisms contribute to neurodegeneration.
Jean-Yves Chatton received his PhD degree in Pharmacology from the University of Lausanne, Switzerland, followed by post-docs at NIH (Bethesda, MD) and in Bern. He is the head of the Cellular Imaging Facility at University of Lausanne and leads a research group in neuroscience with a focus on neuron-glia interactions, mainly related to bioenergetics and ion homeostasis in health and disease. He is actively developing and employing imaging and fluorescence technologies to investigate these issues.
Since 2003 he is the head of the Cellular Imaging Facility (CIF) and since 2021 the director of the Department of Fundamental Neurosciences
Andrea Irazoki studied Genetics at the Autonomous University of Barcelona and initiated her training in basic science at the College of Life Sciences at the University of Dundee. During her training, she identified genes involved in the relationship between mitochondrial function and cell growth, under Dr. Mikael Björklund´s supervision. She graduated in 2015 and moved back to Barcelona, to undertake the MSc in Translational Medicine by the University of Barcelona. During that time, she worked under Prof. Antonio Zorzano and David Sebastián´s supervision, broadening the knowledge on the impact of mitochondrial dynamics and mitophagy in muscle aging. After graduating, she obtained a grant from the same university to carry out her PhD in Biomedicine at the same lab, where she studied the molecular systems linking altered mitochondrial dynamics to muscle inflammation in cellular and in vivo models. After graduating in 2021, she moved to Dr. Lykke Sylow´s lab at the Biomedicinsk Institut of the University of Copenhagen, where she applies her knowledge on mitochondrial biology and inflammation in the context of cancer cachexia. She is now investigating the crosstalk between mitochondrial dysfunction in muscle and adipose tissue, tissue atrophy and systemic inflammation in thermoneutral conditions and upon exercise during cancer cachexia.
Michael was born in South Africa, moving to the UK in 1960. He studied Physiology and Medicine in Oxford, 1971-75, then moved to St George’s Hospital Medical School to complete his clinical training, graduating 1978. he worked in clinical medicine in junior hospital appointments 1978-1981 including a period working at a rural hospital in the Transkei, South Africa. He moved to the UCL Department of Physiology to embark on PhD studies 1981 -1984 with Tim Biscoe as supervisor and mentor. He has stayed at UCL Physiology (now the Department of Cell and Developmental Biology) ever since, first as a Royal Society University Research Fellow, then as Reader and Professor. His early research was electrophysiological with an interest in neurotransmitter receptor biology, but he became interested first in the influence of cell metabolism on excitability and then increasingly fascinated by mitochondrial biology, in the dialogue between cell signalling pathways and mitochondria, in the roles of mitochondria in disease and ultimately in the question of whether mitochondrial pathways represent viable therapeutic targets in a variety of disease states.