Meeting of minds on the mathematics of cell programming

Dr Mark Kotter is a stem cell biologist and neurosurgeon at Cambridge and the founder and CEO of Bit.Bio. The cell coding company’s mission is the efficient and consistent reprogramming of human cells to standardise biomedical research, enable drug discovery and develop next-generation cell therapies.

Dr Ana Martin-Villalba is Professor of Molecular Neurobiology at the German Cancer Research Center. Her group studies the molecular mechanisms underlying normal and malignant stem cell activation in the adult brain.

Anna Marciniak-Czochra, Ana Martin-Villalba and Simon Anders discuss how to figure out trajectories taken by stem cells on their way to differentiation using transcriptomes and methylomes profiles from single cells. Combining statistical data analysis with new transcriptome-structured population models of stem cell self-renewal and differentiation will allow detecting kinematics more complex than those detected by statistical tools alone.

Dr James Briscoe leads the Developmental Dynamics Laboratory at the Francis Crick Institute. His lab works across experimental and computational techniques to understand how morphogen signaling and transcriptional networks specify cell fate in the central nervous system.

James Briscoe will introduce a framework to construct quantitative dynamical models of cell fate decisions from experimental data. He will use data from the differentiation of pluripotent stem cells exposed to different combinations of signaling factors to illustrate how this approach can be used to explain and predict cell fate outcomes.

Benedikt Berninger, Dr rer nat is Professor of Developmental Neurobiology at King’s College London. His group studies how neurogenesis can be initiated in the mammalian brain by converting support cells into induced neurons as well as how neural stem cells integrate into existing networks.

Benedikt Berninger will discuss experimental approaches to reprogramme glial cells into induced neurons in the mouse cerebral cortex. While highlighting the feasibility of inducing neurons with subtype characteristic features in vivo, he will also point out important limitations regarding their maturation.

David Rand is Professor of Mathematics at the University of Warwick. His research develops new mathematical and statistical tools to understand the design and operating principles of biological systems. Recent work on cellular decision making is with James Briscoe and Eric Siggia.

David Rand will follow up James Briscoe's talk with a discussion of the mathematical and statistical underpinning for such an approach to cellular decision-making, including the classification of transitions in dynamical landscapes and fitting them to single cell data.

Dr Ben MacArthur is a Professor of Medicine and Mathematical Sciences at the University of Southampton as well as Director of AI for Science and Government at the Alan Turing Institute. His group blends theory and machine learning to understand biological networks and stem cell dynamics.

Ben explains how theory can help understand cell “fates” and transitions between fates. This analysis shows how common experimentally observed properties of cell lineages emerge naturally from universal dynamical considerations.

Dr Antonio del Sol Mesa is Professor of Bioinformatics at the University of Luxembourg where he leads the Computational Biology Group. His lab develops mathematical and computational tools to understand how molecular networks mediate cellular processes in differentiation and reprogramming.

Antonio Del Sol explains how single cell-based computational models can be developed at different scales of biological organization, including cellular, tissue and organ level, to address challenges in stem cell research and disease modeling.

Jasmin Fisher, PhD, FRSB is Professor of Computational Biology at University College London. Her group has developed an approach called Executable Biology which leverages methods from computer science to understand biological programs and identify molecular mechanisms that underpin cell-fate.

Jasmin Fisher will present an executable modelling framework to study cell fate decision programs during normal development and disease. She will demonstrate how this approach leads to new mechanistic insights and pave the way for improved personalised treatments for cancer patients.

Marius Wernig is a Professor and Co-Director at the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University. His laboratory focuses on the mechanisms of cell lineage specification by direct reprogramming such as the induction of neurons from skin cells. He further seeks to apply reprogramming and genetic engineering to develop novel cell therapies for the brain.

Transcription factors are powerful regulators and inducers of lineage identity. Yet, lineage-specific transcription factors vary in potency to reprogram cells. I will present our latest mechanistic insights into successful neuronal lineage reprogramming which may reveal lessons relevant for reprogramming in general.

Dr Thomas Fink is the founding Director of the London Institute and Charge de Recherche in the French CNRS. He studied physics at Caltech, Cambridge and École Normale Supérieure. His work includes statistical physics, combinatorics and the mathematics of evolvable systems.

Sir John Beddington FRS is a Trustee of the London Institute, Senior Fellow at the Oxford Martin School and Professor of Natural Resource Management at Oxford University. He is a former Government Chief Scientific Adviser. His research applies biology and economics to the sustainable management of natural resources.

Sir Charles Richard Catlow FRS is Professor of Chemistry at UCL and Cardiff University. He is former Director of the Davy-Faraday Research Lab and Wolfson Professor at the Royal Institution. Currently, he serves as Foreign Secretary and Vice-President of the Royal Society and President of the InterAcademy Partnership.

Dr. Robert Beagrie is a new group leader in the Wellcome Centre for Human Genetics at the University of Oxford. He studies chromatin folding and gene expression regulation using both experimental and computational approaches.

Rob Beagrie explores the relationship between DNA folding and gene expression. Is correct folding required for establishing new cell states, maintaining existing states, or both? Is folding more important for some cell types than others, and if so, why?

Gabrielle Dotson is a PhD Candidate in the Department of Computational Medicine & Bioinformatics at the University of Michigan. She previously studied Bioengineering at Stanford University and the National Institutes of Health. Her doctoral research is focused on the dynamics and control of genome organization in human cells.

Successful realization of target cell identity following reprogramming requires specific and efficient cell state perturbations identifiable through a data-guided framework. Coupling time-dependent multi-dimensional data with control theory, data-guided control enables prediction of candidate reprogramming factors and evaluation of the efficacy of driving functional behavior in cells.

Felix Meigel is a Doctoral Researcher at the Max Planck Institute for the Physics of Complex Systems. He works on the statistical physics of stochastic multi-scale dynamics in living systems with applications in cellular decision making, immune response, and bioenergetics.

Felix Meigel explains how cells regulate behaviour by manipulating the transmission of information across scale of spatial organization. He proposes a framework that describes how this mechanism allows cells to interpret fluctuating cues in the context of cell death decisions.

Dr Ulysse Herbach is Chargé de Recherche at the French National Institute for computer science and applied mathematics (Inria). His interests are in mathematical biology, mechanistic machine learning and high-dimensional statistics, especially related to cell fate decision-making.

Ulysse Herbach describes how gene regulatory network inference from single-cell measurements can be seen as a calibration procedure for a mechanistic model driven by transcriptional bursting. Interestingly, cell types can then be recovered as emergent properties of the network.

Prof. Reimer Kühn is Professor of Statistical Physics at King’s College London. His interests lie in the field of statistical mechanics of complex and disordered systems, including the low temperature properties of glasses, phase transitions in disordered systems, and neural networks.

Reimer Kühn describes the deficiences of boolean network models of gene regulation and how a new class of models akin to graded response neural networks can address these deficiences.

Giuseppe Torrisi is a PhD candidate at the Department of Mathematics at King's College London and a Research Fellow at the Center for Regenerative Medicine at the University of Edinburgh. He is interested in the modelling of gene regulation using the tools of disordered systems.

In the Waddington epigenetic landscape metaphor, stable cell types are mapped to stable attractors. Giuseppe Torrisi models gene regulation as an autonomous system and investigates the minimal requirement for the gene regulatory network to support a multiplicity of attractors under noisy conditions.

Dr Renske Vroomans is a Career Development Fellow at the Sainsbury Laboratory at Cambridge. She uses computational models to study the evolution of plant development and the evolution of multicellularity, with a focus on the emergence of novel tissue patterning mechanisms.

Renske Vroomans explains how multiscale evolutionary simulations can be used to shed light on the origins of cellular programmes. She discusses examples from animal body plan patterning, bacterial evolution and multicellularity that show how evolutionary dynamics over long time scales can give rise to genomic and regulatory complexity.

Dr Lee Hazelwood is a physicist and Principal Scientist at bit.bio. His interests lie in the development of functional cell state models, cell identity and regulatory networks.

The reprogramming of cells from iPSCs to differentiated states is based on the activation of key transcription factors (TFs). I will discuss building networks for reprogramming using activation screens and outline the interesting problems for bio-mathematical research.

Dr Sebastian Ahnert is Assistant Professor at the Department of Chemical Engineering and Biotechnology at Cambridge. He works on applications of algorithmic information theory in general, and in particular the insights it provides into structural and functional complexity in biology.

Sebastian gives an overview of progress in our understanding of the large-scale structural properties of genotype-phenotype (GP) maps. The structure of the GP map provides likely distributions of alternative phenotypes under mutation and it is very likely that these insights are relevant to the study of cell fate programming.

Filipe Pereira is an Associate Professor in Molecular Medicine at Lund University in Sweden, and co-founder of Asgard Therapeutics. His group is interested in understanding how hematopoietic cellular identities are specified during development employing cellular reprogramming and to design reprogramming-centric strategies for cancer immunotherapy.

Filipe will discuss technologies for hematopoietic cell fate reprogramming with a focus on progenitors and dendritic cells as well as underlying mechanisms. I will also highlight the potential for generating patient-tailored reprogrammed immune cells and inducing these unique cell identities in vivo, providing new and exciting tools for the fast-paced field of cancer immunotherapy.

Davide Danovi is Director, Cellular Phenotyping at bit.bio and Senior lecturer at King's College London where he develops phenotyping platforms to characterise and quantify cell behaviour. He holds an MD and a PhD and is part of the FLIER (Future Leaders for Innovation Enterprise and Research) group of the Academy of Medical Sciences.

At the Cellular phenotyping team in bit.bio we characterise and quantify cell behaviour using flow cytometry and image analysis. We also develop strategies to capture cells of a specific type within large pools of cells. We look forward to discuss these approaches with particular emphasis on data collation.

Dr Forrest Sheldon is a Junior Fellow at the London Institute. He studied physics at Duke University before completing his PhD at the University of California, San Diego. His work focuses on nonlinear dynamics, disordered systems, inference and neuromorphic computing.

Forrest Sheldon explains how transcription factor screening experiments can be mapped onto a communication problem where sequenced cells form messages. This lets us use tools from information theory to design optimal experiments and decode them to find cell type programs.

Michael Wilkinson has contributed to several areas of theoretical physics. His biological reserch has been primarily in virus genomics, intracellular diffusion, and single-cell mRNA studies.

It will be argued that the variability of single cell mRNA counts for a given gene may be an indication of intermittency of gene expression, rather than differentiation into different cell types. A parametrisation of the data assigns a peak activity and a probability of expression to each gene. This approach has the potential to reveal information about gene regulation networks.

Dr. Carlo Piermarocchi is a Professor of Physics at Michigan State University. His research interests focus on the theory of control of physical and biological systems. He has worked on quantum information theory, cellular signaling networks, and optimization methods for new drug combinations.

Carlo Piermarocchi discusses a model studied in the physics of spin glasses that can reproduce the multi-stable dynamics of cell signaling networks. The model integrates RNA-sequencing data to predict combinations of transcription factors or receptor/ligands that could induce a specific cellular response.

Clive Cookson is the Science Editor at the Financial Times. He studied Chemistry at Oxford, then worked at the Times Higher Education Supplement, spending four years as their American editor in Washington. After a stint at the BBC, he moved to the Financial Times in 1987.

Geoff Carr is the Science and Technology Editor at The Economist. After training as a zoologist, he began working for the magazine in 1991; did a stint as its Tokyo Correspondent; then became Science Editor in 1995. Carr is the author of the dystopian sci-fi thriller, Genesis.

Theo Zenou is a freelance journalist who writes for The Washington Post, The Spectator, the TLS and the New Statesman, among other publications, with a focus on the intersection between politics and culture. He is doing at PhD at Cambridge on 20th century American politics.