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Engineering new interneurons through in vivo glia-to-neuron lineage conversion

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Engineering new interneurons through in vivo glia-to-neuron lineage conversion

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Most of the mechanisms now known to mediate antimicrobial resistance (AMR) are undoubtedly important but are nonetheless obvious. Antibiotics get modified or degraded, they get pumped out, target molecules become mutated, and so on. In this talk, I'll present a series of short vignettes focusing on the much less obvious mediators of AMR, with a particular focus on the biology of Pseudomonas aeruginosa. We'll look at how the presence of other microbes influences antibiotic responses (it does, and not in the way you'd imagine...) and examine how loss of function of the quorum sensing master regulator, lasR (a gene that is commonly mutated in chronic airway infections) impacts on this. I'll put forward a case for lasR being a "keystone gene" in polymicrobial communities. I'll also examine how mutations in a ribosome recycling factor (fusA1) and a global transcriptional regulator (mexT) lead to aminoglycoside resistance. Finally, we'll take a look at biofilms and discuss how the "matrix" that holds biofilms together is more than just a "glue" and instead, acts as a filter to selectively capture and retain key secreted proteins. The possible function of this "matrixome" will be discussed.

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Naughty neighbours and common but "atypical" mechanisms of AMR 

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Naughty neighbours and common but "atypical" mechanisms of AMR 

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Professor at the Department of Biochemistry, University of Cambridge

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Biozentrum, University of Basel

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Eugene Higgins Professor of Molecular Biophysics, Yale University

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Abstract: Lineage reprogramming of glia into induced neurons emerges as an experimental strategy for brain repair. We have recently found that astrocytes (and to a lesser degree oligodendrocyte progenitor cells, OPCs) of the early postnatal cortex can be converted into induced neurons with hallmarks of cortical interneurons. In particular, a phospho-site-deficient mutant of the proneural transcription factor Ascl1 was found to induce the conversion of early cortical astrocytes into neurons that express parvalbumin and are capable of high-frequency action potential firing (Marichal et al., Sci Adv 2024). Here, I will discuss our recent efforts using single cell transcriptomics to uncover the molecular underpinnings of this remarkable response to Ascl1. Furthermore, I will present data based on two-photon live imaging that demonstrate the capacity of induced interneurons to integrate into functional cortical circuits. Overall, our data highlight both the potential and shortcomings of induced neurogenesis for repairing cortical circuits through lineage reprogramming.

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Professor of Developmental Neurobiology, Kings College London

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Professor Giovanna Mallucci is a Founding Principal Investigator at Altos Labs, Cambridge Institute of Science, Cambridge, UK. She was previously Center Director of the UK Dementia Research Institute and van Geest Professor of Clinical Neurosciences at the University of Cambridge. Her lab pioneered the understanding of the role of the Unfolded Protein Response (UPR) in neurodegenerative diseases and its therapeutic manipulation for neuroprotection, including discovering repurposable drugs now in clinical trials. Her interest in neuroprotection led to the discovery of ‘hibernation’ proteins in synapse regeneration that can be targeted therapeutically to prevent neurodegeneration. She is a Fellow of the Academy of Medical Sciences and recipient of the 2021 Potamkin Prize for Research in Pick’s, Alzheimer’s and Related Disorders. In March 2025 she was awarded an Honorary Doctorate (Dr. Honoris Causa) by the Sorbonne University in Paris. Giovanna is a practicing neurologist, specialized in dementia.

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Mechanisms to Medicines in Neurodegeneration

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Mechanisms to Medicines in Neurodegeneration

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Co-Director of the Sir Howard Dalton Centre,

Professor of Chemistry and Life Sciences, University of Warwick

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'Molecular Dynamics of Bacterial Cell Envelopes: From Biogenesis to Resistance

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'Molecular Dynamics of Bacterial Cell Envelopes: From Biogenesis to Resistance

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Department of Mathematical Sciences, University of Bath

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Professor Mark Blaskovich is an ‘antibiotic hunter’ and Director of Translation for the Institute for Molecular Bioscience at The University of Queensland, as well as Director of the ARC Industrial Transformation Training Centre for Environmental and Agricultural Solutions to Antimicrobial Resistance (CEAStAR), and the Community for Open Antimicrobial Drug Discovery (CO-ADD). Blaskovich obtained a PhD in Organic Chemistry from U Waterloo (Canada), followed by a commercial career in medicinal chemistry for 15 years at Molecumetics (USA), CEPTYR (USA) and Mimetica (Brisbane). Since 2010 he has been developing new antibiotics, non-antibiotic therapies and diagnostics to detect and treat resistant bacterial and fungal infections in an academic environment, including multiple industry collaborations focused on antimicrobial resistance. He cofounded CO-ADD, a global antibiotic discovery initiative that has collaborated with over 300 research groups. Blaskovich’s research has led to >160 publications, 11 patent families, and recognition as a Highly Cited Researcher.

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Antimicrobial resistance (AMR) is a rapidly evolving threat to human health, predicted to cause 10 million deaths annually by 2050 [1]. A sparse clinical pipeline mainly populated by new versions of existing antibiotics emphasises the need for novel therapeutic strategies, while the continued clinical use of empirical therapy highlights the need for better diagnostics. This talk will explore some of the different approaches our lab is applying for the discovery new antibiotics and non-traditional antimicrobial agents, including a crowdsourcing initiative designed to uncover novel chemical diversity (the Community for Open Antimicrobial Drug Discovery) and the use of ‘potentiators’ to restore and expand antibiotic activity. I will also present our work on developing a toolkit of antibiotic-derived fluorescent probes to help support fundamental research into interactions between antibiotics and bacteria, and how we think related approaches can be used to develop better diagnostics. .Without significant changes in treating drug-resistant infections, we face a return to a pre-antibiotic era where a simple scratch can kill.

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Detect and Destroy: Collaborative Approaches to Combat Antimicrobial Resistance

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Detect and Destroy: Collaborative Approaches to Combat Antimicrobial Resistance

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Altos Labs - Cambridge Institute of Science

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Institute for Molecular Bioscience, The University of Queensland

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Life defies equilibrium. Key examples are molecular motors that harness chemical energy to drive intracellular transport. Cells self-organise molecular components into intricate structures that enable them to grow, reproduce, and move. At a larger scale, collections of cells follow coordinated pathways of division, differentiation and reorganisation as a single cell develops into a mature organism. The rheology of cell collectives is complex with deformability playing a key role.

Active systems, driven by energy input at the level of individual particles, are also out of thermodynamic equilibrium. Dense active matter shows distinctive collective behaviour: active turbulence, motile topological defects and co-ordinated flows, reminiscent of the rotation of cell clusters or the swirling patterns of a starling murmuration.

In this talk, I will discuss how the physics of active matter is offering fresh perspectives on mechanobiology and developmental biology: from expanding bacterial colonies and the rheology of active cell monolayers to chick morphogenesis.

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The Rudolf Peierls Centre for Theoretical Physics, University of Oxford

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The ability of cells to communicate with each other is fundamental to multicellular life. During development and homeostasis, it is critical that cell signalling is tightly regulated and that the target cell correctly interprets the signal through gene expression changes. We are exploiting the tractability of Drosophila and advances in quantitative imaging to study cell signalling and gene expression dynamics during development. I will present our recent data investigating: 1) how mRNA degradation can play a role in sculpting the expression patterns of some key patterning mRNAs in the early embryo; and 2) how cytonemes (signalling filopodia) regulate short-range BMP signalling to maintain germline stem cells in the Drosophila ovary.

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Faculty of Life Sciences, University of Manchester

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Cell signalling and gene expression

dynamics during development

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Myelin regeneration in the CNS: molecules, mechanisms and medicines

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Myelin regeneration in the CNS: molecules, mechanisms and medicines

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Altos Labs - Cambridge Institute of Science

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Antimicrobial Resistance (AMR) is quickly becoming a global health problem with several million deaths worldwide associated with AMR infections each year. AMR is particularly alarming in the clinical setting due to the generalized use of antibiotics in hospitals, which expedites the evolution of resistant bacteria. AMR can be achieved through different mechanisms. Out of them, conjugative plasmids play an essential role in the spread of AMR among clinical bacteria. These extrachromosomal genetic elements often carry AMR genes and have the ability to be transferred horizontally to nearby cells, promoting the dissemination of AMR genes across bacterial populations. Over the last decade, my group has focused on the study of one of the most concerning groups of resistant bacteria in clinical settings: carbapenemase-producing enterobacteria. In this talk, I will discuss our studies on the ecology and evolution of clinical enterobacteria carrying the carbapenemase resistance plasmid pOXA-48 in a large tertiary hospital in Madrid.

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Plasmid Biology and Evolution Lab, Centro Nacional de Biotecnología – CSIC, Madrid

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Proteins are amazing three-dimensional machines that carry out life’s essential processes. Modern methods in structural biology are enabling us to see these structures at work in ever-increasing molecular detail, and recent innovations in computational methods have revolutionised our ability to design new proteins at will. Yet the most fundamental process of all, how proteins fold and assemble into complex machines, remains mysterious. Errors of protein folding can give rise to devastating diseases that are a major threat to the health of society, such as Alzheimer’s and Parkinson’s diseases and type II diabetes. Given the enormous burden of these, and other, disorders associated with protein misfolding, understanding how proteins fold and why misfolding results in disease has never been more important.

In this seminar I will survey our current knowledge of protein folding; discuss how Alphafold and other computational methods are revolutionising our understanding of protein structure and behaviour; and share some of our newest discoveries in our quest to elucidate how proteins misfold and form beautiful, but deadly, amyloid fibrils associated with disease. Focussing on proteins involved in Alzheimer’s (Ab and tau) and type II diabetes (islet associated polypeptide (IAPP)) I will show how, by combining kinetic analyses of amyloid formation with structural studies using cryoEM and cryoET, we are beginning to learn how the amyloid fold is built in vitro and in situ in human tissue. By screening libraries of approved drugs we have recently discovered small molecules able to change the course of assembly, fuelling our ability to devise new strategies towards combatting disease. Progress in this field is moving apace, yielding a plethora of new discoveries, enormous scientific excitement, and realistic hope that therapies to combat devastating diseases of amyloid assembly will soon be within our grasp.

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Sticky Misfolds: How Amyloid Formation Fuels Disease

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Sticky Misfolds: How Amyloid Formation Fuels Disease

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We want to better understand how cell identity is maintained and reinforced in daughter cells following cell division. To do this we developed approaches that enable the proteins and RNAs that remain chromosome-associated throughout mitosis, to be identified.

I will discuss some of the results of these studies as well as our future plans.

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Hubrecht Institute, Developmental Biology & Stem Cell Research

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Achilles Kapanidis studied Chemistry at the Aristotelian University of Thessaloniki (Greece) and completed his MSc in Food Chemistry and his PhD in Biological Chemistry at Rutgers University (USA). After holding research scientist positions in single-molecule biophysics at the Lawrence Berkeley National Lab (Berkeley, California) and at the University of California at Los Angeles (UCLA), he became a senior lecturer at Oxford University, and then a Professor of Biological Physics; Prof Kapanidis has also been an ERC grant holder and is currently a Wellcome Trust Investigator.

Prof Kapanidis is leading a group of physical and biological scientists (the “Gene Machines” group) which studies microbial biological machinery in gene expression, maintenance, and regulation, with a focus on gene transcription and DNA repair. The main tool of the group is single-molecule fluorescence microscopy coupled with advanced image and time-series analysis; the past few years, his group has been working on rapid and ultrasensitive detection of antibiotic resistance and pathogenic viruses, including influenza and coronaviruses. Prof Kapanidis had also been pursuing miniaturized single-molecule imaging, a project that culminated in the formation of the Oxford Nanoimaging spin-out, and for which he has shared the 2019 BBSRC Innovator of the Year award. Finally, Prof Kapanidis has been a key person for the establishment of the Oxford Kavli Institute of Nanoscience Discovery, a new interdisciplinary institute focused on using cutting-edge physical approaches to study biological mechanisms in living cells.

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Imaging-driven bacteriology: from single molecules to AMR detection

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Imaging-driven bacteriology: from single molecules to AMR detection

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Erin Schuman was born in 1963 in San Gabriel, California (USA), and obtained her Bachelor’s degree from the University of Southern California and her Ph.D. in Neuroscience from Princeton University. Schuman carried out her postdoctoral work in Molecular and Cellular Physiology at Stanford University. In 1993 she joined the Biology faculty at the California Institute of Technology.  In 1997 she was also appointed as an investigator of the Howard Hughes Medical Institute. In 2009 she was recruited as a founding director of the Max Planck Institute for Brain Research and moved to Frankfurt, Germany, where she heads the Department of Synaptic Plasticity.

She is an elected member of EMBO, the German Academy of Sciences Leopoldina, the US National Academy of Sciences, and of the American Academy of Arts and Sciences. She received the Louis-Jeantet Prize for Medicine, the FENS-Kavli-ALBA Diversity Prize, the EMBO Women in Science Award, the Rosenstiel Award, and the Brain Prize. Schuman’s major contribution to science has been to understand how proteins are supplied to brain cells, particularly in their axons and dendrites.

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Max Planck Institute for Brain Research, Frankfurt, Germany

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Faculty of Medicine, Institute of Clinical Sciences, Imperial College London

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Enhancer Resetting: How chromatin translates signals into transcription

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Enhancer Resetting: How chromatin translates signals into transcription

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Brian Hendrich received his PhD from Stanford University working on X chromosome inactivation with Huntington Willard. He joined the lab of Adrian Bird at the University of Edinburgh for postdoctoral work and participated in the discovery and characterisation of a family of methyl-CpG binding proteins in mammals. In 2001 he started his own laboratory at the University of Edinburgh. In 2008 he moved to the Wellcome Trust Centre for Stem Cell Research in Cambridge. He is currently a Principal Research Associate and Director of the PhD Programme in Stem Cell Biology and Medicine for the Cambridge Stem Cell Institute. He can often be found cycling the roads of East Anglia, in search of a hill.

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Astbury Centre for Structural Molecular Biology,

University of Leeds

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Department of Physics, University of Oxford

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New forms of ultrasensitive fluorescence imaging have opened new frontiers for understanding the mechanisms of bacterial cells and for the rapid detection of bacterial pathogens.

Some of these imaging methods rely on the ability to detect single protein molecules in living cells; I will discuss examples of our in vivo single-molecule work in bacteria, including our latest work of understanding the roles of the universal and multi-functional transcription factor NusG, a protein that couples transcription and translation.

Other imaging methods provide high-content information that help bacterial detection; along these lines, I will present our efforts to rapidly detect different bacterial species, as well as the presence of antimicrobial resistance (AMR) in clinical samples. Our methods and biological observations are general and apply to many systems and organisms.

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Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge

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“Learning from genetic disorders: A cytoplasmic version of FoxG1 transcription factor drives local decisions in neurons ”

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“Learning from genetic disorders: A cytoplasmic version of FoxG1 transcription factor drives local decisions in neurons ”

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Corinne Houart is Professor of Developmental Neurobiology, MRC Centre for Neurodevelopmental Disorders and Vice Dean Research of the Faculty of Psychiatry, Psychology and Neuroscience. She is on the editorial board of leading developmental biology journals, board member of funding bodies, EMBO member and recipient of the MRC Suffrage Science Award. Prof. Houart got her PhD at the University of Brussels in 1992, working on gene regulation in cancer. She dedicated her postdoctoral training to exploring early forebrain development in zebrafish, at the University of Oregon in the USA, the then epicentre of zebrafish genetics. She started her own lab in 2002, at King’s College London. Her team unveiled key mechanisms of fate specification shaping forebrain regionalisation and is currently identifying the evolutionary aspects of these early decisions. They aim to understand the signalling integration controlling telencephalic across species using animals and 3D cell culture. Her group developed more recently a second research direction, using original approaches to understand local mRNA regulation driving neuronal maturation. Both research directions led to findings opening therapeutic avenues for neurodevelopmental and neurodegenerative disorders

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The Wellcome Trust Genome Campus, Cambridge

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Mechanisms underlying functional neuron-microglia interactions driven by gamma frequency neuronal network oscillations

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Mechanisms underlying functional neuron-microglia interactions driven by gamma frequency neuronal network oscillations

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Avian magnetoreception – a radical sense of direction?

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Avian magnetoreception – a radical sense of direction?

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Biochemistry Department, University of Oxford

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I have spent most of my life in the Department of Chemistry at the University of Oxford, first as a student, then as a Junior Research Fellow (1982–83), and now as Professor of Chemistry and Fellow of Corpus Christi College. My only time away from Oxford was a postdoctoral fellowship at the University of Groningen (1980–82). Over the years I have worked on a number of topics around magnetic resonance and the effects of electron and nuclear spins on chemical reactivity, an area known as Spin Chemistry. These include spin hyperpolarization, protein structure and folding, photosynthetic energy conversion, and NMR methodology. Since about 2005 I have been having fun trying to unravel the biophysical mechanism that allows migratory songbirds to detect the direction of the Earth’s magnetic field as an aid to navigation.

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Small migratory songbirds are extraordinary navigators: weighing less than 30 g, they fly thousands of kilometres between their breeding and wintering grounds, alone and at night, with centimetre precision. To do this they use the sun and the stars, olfaction and landmarks but it is clear that they can also perceive the direction of the Earth’s magnetic field. Despite more than 50 years of research, the biophysical mechanism of this remarkable magnetic sense remains obscure. In this lecture, I will discuss the proposal that the birds’ magnetic compass relies on a quantum mechanism in their eyes. Specifically, the unique properties of light-induced radical pairs in cryptochrome proteins in photoreceptor cells could allow chemical sensing of magnetic interactions orders of magnitude weaker than previously thought possible.

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Epigenetic memory and the germline cycle: the tales of erasure, maintenance and stability

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Epigenetic memory and the germline cycle: the tales of erasure, maintenance and stability

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Nobel Laureate                Prof Richard Henderson 

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Nobel Laureate                Prof Richard Henderson 

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MRC Laboratory of Molecular Biology, Cambridge University.

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Prof Molly M Stevens FREng FRS is Professor of Biomedical Materials and Regenerative Medicine and the Research Director for Biomedical Material Sciences in the Department of Materials, in the Department of Bioengineering and the Institute of Biomedical Engineering at Imperial College London.

Prof Stevens’ multidisciplinary research balances the investigation of fundamental science with the development of technology to address some of the major healthcare challenges. Her work has been instrumental in elucidating the bio-material interfaces. She has created a broad portfolio of designer biomaterials for applications in disease diagnostics and regenerative medicine. Her substantial body of work influences research groups around the world (>380 publications, h-index 86, >30k citations, 2018 Clarivate Analytics Highly Cited Researcher in Cross-Field research).

Prof. Stevens holds numerous leadership positions including Director of the UK Regenerative Medicine Platform "Smart Acellular Materials" Hub and Deputy Director of the EPSRC IRC in Early-Warning Sensing Systems for Infectious Diseases.

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Designing the biomaterial interface for therapeutics and biosensing

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Designing the biomaterial interface for therapeutics and biosensing

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This talk will provide an overview of our recent developments in bio-instructive, self-assembling and gradient materials for applications in regenerative medicine with focus on establishing translational pipelines to bring our innovations to the clinic [1]. I will present how we are using remote fields to engineer complex 3D architectures that mimic anisotropic and multiscale tissue structures and generate spatially arranged bioinstructive biochemical cues, such as acoustic stimulation to produce engineered muscle with bundles of aligned fibres [2]. I will discuss recent developments in our tunable nanoneedle arrays for multiplexed intracellular biosensing at sub-cellular resolution and modulation of biological processes [3], and will talk about our portfolio of nanoparticle-based sensing probes for diagnosing and monitoring infectious and non-communicable diseases with integration to smartphone technology for mHealth approaches [4, 5]. Finally, I will present our advances in Raman spectroscopy characterisation techniques for high-throughput label-free characterization of single nanoparticles (SPARTA™) which is becoming an integral tool for the design of advanced nanotherapeutics [6].

[1] J. P. K. Armstrong… M. M. Stevens. “A blueprint for translational regenerative medicine.” Science Translational Medicine. 2020. 12(572): eaaz2253.

[2] J. P. K. Armstrong,… M. M. Stevens. “Engineering anisotropic muscle tissue using acoustic cell patterning.” Advanced Materials. 30(43): 1802649.

[3] C. Chiappini…  M. M. Stevens, E. Tasciotti. “Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization.” Nature Materials. 2015. 14: 532

[4] C. N. Loynachan… M. M. Stevens. “Renal clearable catalytic gold nanoclusters for in vivo disease monitoring.” Nature Nanotechnology. 2019. 14: 883–890.

[5] C. S. Wood, … M. M. Stevens. “Taking connected mobile-health diagnostics of infectious diseases to the field.” Nature. 2019. 566: 467-474.

[6] J. Penders… M. Stevens. “Single particle automated Raman trapping analysis.” Nature Communications. 2018, 9: 4256.

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Imperial College London

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Selina Wray is a Professor of Molecular Neuroscience and  Alzheimer's Research UK Senior Research Fellow in the Department of Neurodegenerative Disease at UCL Queen Square Institute of Neurology.

Selina received her degree in Biochemistry and Biological Chemistry from the University of Nottingham in 2004, before undertaking PhD training in Dr Diane Hanger’s laboratory at the Institute of Psychiatry, Kings College London.  Selina was awarded her PhD in 2008 and subsequently joined the laboratory of Professor John Hardy at UCL Queen Square Institute of Neurology before eventually setting up her own lab at UCL.

Selina’s work is focussed on the use of induced pluripotent stem cell (iPSC) technology to model dementia,  working closely with clinical colleagues to obtain samples from participants with rare, genetic forms of dementia and using these to understand the molecular basis of Alzheimer's Disease and Frontotemporal Dementia. In recognition of her research and public engagement, Selina was awarded the 2018 ARUK David Hague Early Career Investigator of the Year award and the 2014 Red Magazine Woman of the Year award in the Pioneer category.

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Human stem cell models of Alzheimer’s disease and frontotemporal dementia

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Human stem cell models of Alzheimer’s disease and frontotemporal dementia

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The development of human induced pluripotent stem cells (iPSC) and their subsequent differentiation into neurons has provided new opportunities for the generation of physiologically-relevent in vitro disease models.  I will present our work using iPSC to modal familial Alzheimer's Disease (fAD) and Frontotemporal Dementia (FTD).  We have investigated the mutation-specific effects of APP and PSEN1 mutations on Abeta generation in neurons generated from individuals with fAD, revealing distinct mechanisms that may contribute to clinical heterogeneity in disease.  I will also discuss our  work to understand the developmental and pathological changes to tau that occur in iPSC-neurons, particularly the challenges of understanding tau pathology in a developmental system, tau proteostasis and how iPSC-neurons may help us identify early signatures of tau pathology in disease.

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Department of Neurodegenerative Disease
University College London

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Breaking symmetry in the brain: from genes to circuits and behaviour

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Div of Biosciences
University College London

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Thomas Lecuit is a group leader at IBDM in Marseille and studies the biophysical principles of cell and tissue morphogenesis. He is founding director of the Turing Centre for Living Systems, an interdisciplinary centre studying the complexity and self-organization in biology. He is a Professor at the Collège de France in Paris, chair “Dynamics of Living Systems”, an elected member of the EMBO, French Académie des Sciences and Academia Europaea.

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Dynamics of Living Systems
Collège de France

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Jonathan is Professor of Epigenomics at the University of Exeter Medical School where he heads the Complex Disease Epigenomics Group and is co-head of the Department of Clinical and Biomedical Sciences. He graduated with a degree in Human Sciences from Oxford University, where he took a particular interest in cannibalism, before undertaking his PhD in psychiatric genetics at the MRC Social, Genetic & Developmental Psychiatry Research Centre at the Institute of Psychiatry, King's College London. After spending three years as a Canadian Institutes of Health Research (CIHR) postdoctoral fellow at the University of Toronto, he returned to the Institute of Psychiatry to establish the Psychiatric Epigenetics group. He was appointed as Professor of Epigenomics at the University of Exeter in September 2012.

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Professor of Epigenomics at the University of Exeter Medical School

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MRC Laboratory of
Molecular Biology Cambridge