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Theory of Living Matter Group

Events

We organise different types of regular events, taking place about once per month. In the more formal regular meetings we will have one or two high profile speakers with an experimental or theoretical background. These talks are aimed to be understandable for a broad audience. Further, in more informal meetings with series of talks from experimental biologists that present their work where they believe that a contribution by theoretical modelling can improve the quality of their research. Finally, theory meetings will discuss theoretical approaches, and offer a forum to theorists to present formalisms and methodologies. Presentations of Theory Meetings will aim to be understandable to a broad and interdisciplinary audience, and all interested biologists are welcome and encouraged to attend.


Past events

Pub Tutorial with Pierre-François Lenne

Thursday, 20th April 2017 from 6-8pm
The Old Bicycle Shop, 104 Regent Street, Cambridge CB2 1DP

Theory of Living Matter is back with an informal pub meeting. In this meeting with Pierre-François Lenne, we will focus on Optical trapping and optical tweezers. The talk will be understandable for a broad scientific audience.

Light is essential for biological imaging but it can also be used to trap and exert forces on objects. The first optical trapping system simply consisted of tightly focusing a laser beam using a good optical lens. I will briefly review the history of optical trapping and describe the basic physical principles of optical tweezers. I will then describe a few popular and exotic implementations of the technique. I will finally show applications of the use of optical forces in biology, from single molecule to tissue mechanics.

9th General Meeting of the TLM network

28th March 2017, 6pm
Main lecture theatre, Sainsbury Laboratory, Bateman St, Cambridge CB2 1NN

This meeting focused on statistical methods in quantitative and computational biology. Our speakers in this meeting will be Dr Ben MacArthur, from the University of Southampton, and Dr Radu Zabet from the University of Essex. Both talks will be understandable for a broad scientific audience.

Dr Zabet talked about Quantitative models for transcription factor binding to the DNA.

In all kingdoms of life, transcription factors (TFs) are proteins that bind to specific sites on the DNA and control the expression of their target genes. Understanding where TFs bind to genome and what controls this process is pivotal to better understanding gene regulation and, consequently, to enhance our understanding of the cellular response to developmental, physiological, environmental or disease signals. We developed a statistical thermodynamics framework to model binding profiles of TFs in eukaryotic systems. One of the main advantages of the model is that it uses mathematical approximations, which allows it to predict whole genome ChIP-seq profiles in mammals within hours. Using the actual occupancy data in form of ChIP-seq profiles, we were able to estimate the number of molecules bound to the DNA for five Drosophila melanogaster TFs (Bicoid, Caudal, Giant, Hunchback and Kruppel) during early embryonic development. Our results support a model where the majority of the molecules are diffusing and are not engaged in direct interactions with the DNA (only between 10-30% of the molecules were bound to the DNA). In addition, for Bicoid and Caudal we were able to predict their binding profiles with high accuracy. Finally, we confirm that ChIP-seq experiments produce quantitative information on the level of binding of TFs to the DNA and our model is able to capture this aspect. In particular, the height of the ChIP-seq peak contains information on the amount of TF in the nucleus.

Dr MacArthur's talk was about Statistical Models of Stem Cells.

There is a long-running debate amongst stem cell biologists over stochastic versus instructive models of stem cell dynamics. In this talk I will discuss the background to this problem and show some recent data from differentiation of pluripotent stem cells toward neural progenitors which favours the stochastic perspective. Along the way I will also discuss some of the problems associated with making measurements of stochastic systems and I will show how the act of measuring using fluorescence reporters can disturb the dynamics of the system being measured, thereby presenting a basic measurement problem in cell biology. I will summarise with some suggested areas for further work that may benefit from increased collaboration between experimentalists, physicists and mathematicians.

Pub tutorial

November 2nd from 6-8pm, Panton Arms, 43 Panton St, CB2 1HL

In this tutorial, Gopi Shah (CRUK CI) and Vikas Trivedi (Genetics department) presented an introduction to Light Sheet Microscopy

Light sheet microscopy has emerged as the imaging tool of choice since its first successful demonstration for live imaging of biological specimen in 2004. At the core of this technique lies the orthogonality of illumination and detection axes, unlike the more conventional geometries, such as the ones in confocal or epi-illumination microscopes, where the two light paths are co-axial. The illumination is achieved through a sheet of light (instead of a beam as used in confocal) and the illuminated plane is imaged onto a camera, thereby giving this technique its commonly used name Selective Plane Illumination Microscopy (SPIM). Such an arrangement achieves high performance in imaging speed, multi-sided illumination and detection, high signal to background and diffraction-limited resolution, while inducing low photodamage, thereby allowing extended 4D imaging of biological processes. In this workshop we will provide a general overview of the technique, its historical development, current advancements- both commercial and custom-built, as well as the future and scope of this imaging technique as seen through the eyes of two long term users/developers of light-sheet microscope.<

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General meeting of the TLM network

June 28th from 6-8pm, Main lecture theatre, Sainsbury Laboratory, Bateman St., Cambridge CB2 1NN

This meeting will focus on transcriptional and epigenetic mechanisms underlying cellular decision making. Our speakers in this meeting will be Professor Martin Howard, from the John Innes Centre (Norwich), and Dr James Locke from the Sainsbury Laboratory. Both talks will be understandable for a broad scientific audience.

We begin with a talk by Professor Howard on Dissecting quantitative epigenetics using mathematical modelling and experiments

We are studying the mechanistic basis of epigenetic regulation in the Polycomb system, a vital epigenetic silencing pathway that is widely conserved from flies to plants to humans. We use the process of vernalization in plants in our experiments, which involves memory of winter cold to permit flowering only when winter has passed via quantitative epigenetic silencing of the floral repressor FLC. Utilising this system has numerous advantages, including slow dynamics and the ability to read out mitotic heritability of expression states through clonal cell files in the roots. Using mathematical modelling and experiments (including ChIP and fluorescent reporter imaging), we have shown that FLC cold-induced silencing is essentially an all-or-nothing (bistable) digital process. The quantitative nature of vernalization is generated by digital chromatin-mediated FLC silencing in a subpopulation of cells whose number increases with the duration of cold. We have further shown that Polycomb-based epigenetic memory is indeed stored locally in the chromatin (in cis) via a dual fluorescent labelling approach. I will also discuss how further predictions from the modelling, including opposing chromatin modification states and physical coupling of activators and de-repressors, have been verified. Finally, I will discuss how such digital control can be integrated with more conventional analogue transcriptional regulation to generate chromatin states that are either instructive or responsive depending on the strength of the analogue regulation.

Dr Locke will talk about Mechanism and function of circadian clock coupling.

The circadian clock orchestrates gene regulation across the day/night cycle in a wide range of organisms, from cyanobacteria to mammals. The core mechanism of the clock has been worked out, with one or more feedback loops generating the 24 h oscillation in gene expression. However, the clock can drive and receive input from diverse cellular processes, including the cell cycle, stress response, and metabolism. How does the clock integrate signals from these diverse inputs to produce a robust output? How is clock information coordinated between cells? To address these questions we are using the common tools of mathematical modelling, synthetic biology, and single cell time-lapse microscopy on two model organisms, the cyanobacterium Synechococcus elongatus, and the model plant Arabidopsis. I will present our work examining how and why clocks are coupled, both between cells and to other gene networks.

After the talk there will be plenty of time for informal discussions. We will serve some snacks and wine.

SLCU Seminar

February 24th 2016 at 4pm, Auditorium of the Sainsbury Laboratory

Naama Barkai (PI Barkai Lab, Weizmann Institute of Science) will give a talk on Expression homeostasis during DNA replication. Tea will be served in the Atrium after the seminar.

TLM Tutorial

February 3rd 2016 at 6pm, Panton Arms, 43 Panton St, CB2 1HL

In this tutorial, Joe Guy will teach us about Magnetic Resonance Imaging (MRI), a method which is not only used to image the inner anatomy of human patients, but has a wide range of applications in biology and biomedicine. Joe will in particular address the physics and information theoretical background, how the information from electromagnetic interactions between a radio source and atoms in biological tissue is transformed into a spatial image.

Magnetic resonance imaging (MRI) is a technique that provides highly detailed images of living systems. It allows doctors and scientists alike to peer inside a living body, revolutionizing both science and medicine. But how does it work? Clever timings of radio waves combined with magnetic fields of varying strength cause subatomic particles to absorb and transmit energy in a way that can be detected an formed into an image. Here I explain this process in detail all the way from the radio wave to the pixel on the screen, requiring no background in physics, mathematics, chemistry, or biology to understand.

After the tutorial there will be plenty of time for informal discussions. We will serve some snacks and there will be opportunities to order food and drinks.

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General meeting of the TLM network

December 2nd from 6-8pm, Main lecture theatre, Sainsbury Laboratory, Bateman St., Cambridge CB2 1NN

This meeting will be focussed on gene regulation and (RNA-based) epigenetic marks. We will begin with a talk by John Marioni (EMBL EBI) who will be talking about Using single-cell genomics to study early development.

Gastrulation and the specification of the three germ layers are key events in animal development. However, molecular analyses of these processes have been limited due to the small number of cells present in gastrulating embryos. With recent developments in the field of single-cell biology however, it is now possible to overcome these limitations and to characterize, for the first time at the single-cell level, how cell fate decisions are made.

In this presentation I will discuss data generated to study cell fate specification in mouse, as well as the computational strategies we have developed to model such data. I will then illustrate how these data can provide insight into germ layer specification and early erythropoiesis.

Eric Miska (Gurdon Institute) will be talking about Non-Coding RNA: from immunity to epigenetic inheritance.

Since August Weismann (1834-1914) formulated the distinction between innate and acquired characteristics at the end of the 19th century, the debate relating to the inheritance of acquired traits has raised many controversies in the scientific community. Following convincing arguments against (e.g. William Bateson) this debate was then set aside by the majority of the scientific community. However, a number of epigenetic phenomena involving RNA, histone modification or DNA methylation in many organisms have renewed interest in this area. Transgenerational effects likely have wide-ranging implications for human health, biological adaptation and evolution, however their mechanism and biology remain poorly understood. We recently demonstrated that a germline nuclear small RNA/chromatin pathway can maintain epi-allelic inheritance for many generations in C. elegans. This is a first in animals. We named this phenomenon RNA-induced epigenetic silencing (RNAe). We are currently further characterizing the mechanism of RNAe. In addition, we are testing the hypothesis that RNAe provides a transgenerational memory of the environment (“Lamarckism”). We are currently exploring related phenomena in mice. We are also working towards establishing iPS cells differentiating into germ cells as a model to study the mechanism of transgenerational epigenetic inheritance.

After the talks there will be plenty of time for informal discussions. We will serve some snacks and wine.

TLM pub meeting

October 21st 2015 at 6pm, Panton Arms, 43 Panton St, CB2 1HL

In this meeting we will focus on dynamic changes in the epigenome. We will have two talks, an experimental talk on novel single-cell methods and a more theoretical talk on the dynamics of DNA methylation in primed embryonic stem cells. Both talks will be understandable for a broad scientific audience.

In the first part of the meeting Heather Lee (Babraham Institute) will give a talk on Novel single-cell sequencing methods link transcriptional and epigenetic heterogeneity.

Every cell in your body contains the same genetic information, but access to this information is restricted such that specialised cell types are generated in each organ. This is achieved by epigenetic mechanisms including DNA methylation. We have recently developed a new method for studying genome-wide DNA methylation in single cells, revealing epigenetic heterogeneity in pluripotent stem cells. By combining this technique with analysis of gene expression in the same single cell (parallel single–cell genome–wide methylome and transcriptome sequencing), we have been able to reveal associations between transcriptional and epigenetic variations, allowing us to study the complexity of epigenetic regulation at unprecedented detail. These methods hold great promise for our understanding of developmental biology and for clinical applications.

Then, after a short break, Steffen Rulands (Department of Physiology, Development and Neuroscience) will talk about Global oscillations in DNA methylation in primed embryonic stem cells.

Mouse embryonic stem cells (mESCs) primed for differentiation exist in a state of dynamic equilibrium characterised by stochastic switching between transcriptional states. Recent advances in single-cell methods highlighted the heterogeneous and dynamic nature of DNA methylation in these cells. Combining novel single-cell sequencing methods with mathematical modelling we discovered global oscillations in mESC DNA methylation affecting most parts of the genome including distal enhancers. These oscillations are dependent on DNA methylation turnover by DNMT3 and TET enzymes. We hypothesise that oscillations in DNA methylation are associated with increased transcriptional heterogeneity, thereby contributing to lineage priming in cells poised for differentiation.

After the talk there will be plenty of time for informal discussions. We will serve some snacks and there will be opportunities to order food and drinks.

TLM pub meeting

July 9th 2015 at 6pm, Panton Arms, 43 Panton St, CB2 1HL

In this informal meeting we will have a talk by Alexandra Kabla (Engineering Department) will give a talk on Morphogenesis, cell migration and cell rearrangements.

Cell migration relates to the active motion of a cell with respect to its direct environment, being a flat substrate, extra-cellular matrix or other cells. Single cell migration has been extensively studied in vitro and in vivo, and it is now clear that cells adopt different strategies depending on a number of environmental cues. By contrast, the case of cells migrating within populations of other motile cells remains challenging to tackle. Yet this is the process driving the early stages of animal development as well as certain pathologies such as cancer metastasis. We will review experimental techniques and conceptual tools commonly used to characterise and understand the dynamics of large cell populations. We will focus more specifically on two classes of cell motions: (i) collective cell migration, during which a coordinated group of cells migrate with respect to a support while largely preserving links with neighbours, and (ii) cell intercalation, where cells move relative to their neighbours and drive convergent-extension, a large scale tissue reorganisation process, without the need for an external support to migrate onto.

After the talks there will be plenty of time for informal discussions. We will serve some snacks and there will be opportunities to order food and drinks.

More information and registration

General meeting of the TLM network

June 4th from 6-8pm, Main lecture theatre, Sainsbury Laboratory, Bateman St., Cambridge CB2 1NN

This meeting will be jointly organised with NanoDTC and it will be focussed on the biophysics of subcellular structures and of cells contributing to morphogenesis. On this special occasion we have two external speakers who are renowned experts in studying the dynamics of the cytoskeleton and of developing tissues: Yohanns Bellaiche (Institut Curie, CNRS, Paris) will be talking about Cell division and epithelial tissue morphogenesis.

Questions related to embryo shape or morphogenesis have haunted developmental biologists for decades. Recent advances in imaging, cell biology, signal transduction and biophysics have framed the study of tissue morphogenesis in terms of collective cell dynamics and the interplay between biochemical and mechanical processes. Recent findings have confirmed that proliferative epithelial tissues reshape via morphogenetic processes such as cell shape change and cell rearrangements. Yet cell division remodels adherent junctions and modulates both tissue mechanics and tissue dynamics. Therefore its role and interplay with the other morphogenetic processes need to be understood to decipher the mechanisms of tissue morphogenesis. Moreover, given the large size of some proliferative tissues, challenging questions can be addressed: How do local and long-range mechanical effects contribute to tissue dynamics? How do the combinations of several signaling pathways or gene expression patterns specify distinct local cell dynamics leading to the emergence of several morphogenetic movements within a given tissue? During my talk I will describe some of our latest works that aim to understand the mechanisms of mitotic

Ewa Paluch (Laboratory of Molecular Cell Biology, UCL) will be talking about Actin Cortex mechanics in Cell Morphogenesis.

After the talk there will be plenty of time for informal discussions. We will serve some snacks and wine.

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Biological and Statistical Physics Discussion Group (BSDG)

28th May 2015, TCM Seminar Room (530, Mott building), Cavendish Laboratory
Website

Yixin Kirsty Wan (DAMTP) will be talking about Powers of two (flagella).

This discussion group aims to share research interests in Theoretical Biology and learn from each other in the form of weekly meetings. Contact Salvatore Tesoro (st590@cam.ac.uk) to be added to the BSDG mailing list and receive more information.

Biological and Statistical Physics Discussion Group (BSDG)

14th May 2015, TCM Seminar Room (530, Mott building), Cavendish Laboratory
Website

Sebastian Ahnert (TCM, Cavendish Laboratory) will be talking about A tractable genotype-phenotype map for biological self-assembly.

The mapping between biological genotypes and phenotypes is central to the study of biological evolution. We introduce a rich, intuitive and biologically realistic genotype– phenotype (GP) map that serves as a model of self-assembling biological structures, such as protein complexes, and remains computationally and analytically tractable. Our GP map arises naturally from the self-assembly of polyomino structures on a two-dimensional lattice and exhibits a number of properties: redundancy (genotypes vastly outnumber phenotypes), phenotype bias (genotypic redundancy varies greatly between phenotypes), genotype component disconnectivity (phenotypes consist of disconnected mutational networks) and shape space covering (most phenotypes can be reached in a small number of mutations). We also show that the mutational robustness of phenotypes scales roughly logarithmically with phenotype redundancy and is positively correlated with phenotypic evolvability. Although our GP map describes the assembly of disconnected objects, it shares many properties with other popular GP maps for connected units, such as models for RNA secondary structure or the hydrophobic-polar (HP) lattice model for protein tertiary structure. The remarkable fact that these important properties similarly emerge from such different models suggests the possibility that universal features underlie a much wider class of biologically realistic GP maps. A further property of the polyomino GP map is that the modularity, symmetry and structural complexity of the phenotype can be quantified rigorously. We can therefore use our GP map to study the emergence of these phenotypic properties in the course of biological evolution, and present results on the distribution of complexity in phenotypes, which are intimately linked with the properties of genotype-phenotype maps.

This discussion group aims to share research interests in Theoretical Biology and learn from each other in the form of weekly meetings. Contact Salvatore Tesoro (st590@cam.ac.uk) to be added to the BSDG mailing list and receive more information.

Second Tutorial

April 29th from 12-2pm, Theory of Condensed Matter seminar room, Mott Building, Cavendish Laboratory, 19 JJ Thomson Avenue, Cambridge CB3 0HE

In this tutorial Edouard Hannezo will give an Introduction to the Modelling of Forces in Biological Tissues. The lecture is intended to be understandable for a broad audience with an interest in and basic knowledge of mathematics. No preliminary knowledge in non linear dynamics will be required. However, participants are supposed to have basic training in mathematical methods, especially differential equations and some linear algebra.

Forces play an essential role in biological processes such as development, cancer and homeostatic tissue regeneration. In this tutorial I will give an introduction to the theoretical methods that can be used to understand these forces and the ensuing tissue dynamics.

After the talk there will be plenty of time for informal discussions. We will serve some snacks.

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TLM pub meeting

March 18th 2015 at 6pm, The Brew House, 1 King St, CB1 1LH Cambridge

In this informal meeting we will have two talks on chromatin dynamics, an experimental talk and a theoretical talk. Both talks are intended to be understandable for a broad audience. Andrew Travers (MRC Laboratory of Molecular Biology) will give a talk on Why DNA?, which will also serve as a general introduction to the field.

The proposal of a double-helical structure for DNA over 60 years ago provided an eminently satisfying explanation for the heritability of genetic information. But why is DNA, and not RNA, now the dominant biological information store? I argue that, in addition to its coding function, the ability of DNA, unlike RNA, to adopt a B-DNA structure confers advantages both for information accessibility and for packaging. The information encoded by DNA is both digital - the precise base sequence specifying, for example, aminoacid sequences - and analogue. The latter determines the sequence-dependent physicochemical properties of DNA, for example its stiffness and susceptibility to strand separation. Most importantly DNA chirality enables the formation of supercoiling under torsional stress. I review recent experimental evidence suggesting that DNA supercoiling, especially that generated by DNA translocases, is a major driver of gene regulation and patterns of chromosomal gene organisation, and in its guise as a promoter of DNA packaging enables DNA to act as an energy store to facilitate the passage of translocating enzymes such as RNA polymerase.

Then, after a short break, Christopher Verstreken (Department of Physics and Stem Cell Institute) will talk about Building a DNA sandcastle: developing a granular model to describe large scale chromatin structure and dynamics .

Aiming to determine the conformation of chromatin on a global scale, this is a computational model that approaches the nucleus as a system of independent yet interacting domains, similar to grains of sand. The mechanical behaviour of a nucleus under compression could therefore provide information about its structure and dynamics.

After the talks there will be plenty of time for informal discussions. We will serve some snacks and there will be opportunities to order food and drinks.

More information and registration

Putting the 'q' back in qPCR

5th March 2015, Homerton College
Website

On Thursday 5th March at Homerton College Cambridge, we are hosting a seminar on Putting the 'q' back in qPCR: State-of-the art advances in gene expression measurement. All levels are welcome!

Since its inception the real time quantitative polymerase chain reaction, or more commonly ‘qPCR’, has been an indispensable technique in almost every molecular biology laboratory. RT-qPCR has completely revolutionized what we know about the nature and regulation of our genes; however, many scientists in academia, industry and healthcare do not know how to make full use of its potential. Leading expert Dr David Sugden from qStandard and King’s College London will cover the common mistakes and challenges of RT-qPCR, such as those of standardization, as well as the inaccuracies and misinterpretations that have long been propagated in the wide-scale application of the technique. In addition, Dr Fernando Calero-Nieto, a senior scientist from the Göttgens lab at the University of Cambridge, will talk about the virtues and difficulties of single-cell RT-qPCR and the novel opportunities it has created in blood stem/progenitor cell research. The talks will be followed up with a networking session in which wine and food will be provided. There will also be an equipment and reagents showcase and a chance to interact with academic and industry specialists in this technique.

Please register at: www.cambioscience.com (so we can be sure to have enough wine and food for everyone!)

Biological and Statistical Physics Discussion Group (BSDG)

5th March 2015, TCM Seminar Room (530, Mott building), Cavendish Laboratory
Website

Francois Peaudecerf (University of Cambridge) will be talking about Algal-bacterial interactions at a distance.

Microbial interactions are often predicated on metabolism: e.g. auxotrophs depend on nutrients made by other microbes. Many algae are vitamin auxotrophs, with several known species requiring exogenous vitamin B12. This vitamin must be obtained from bacteria, as only they can synthesise it. Laboratory experiments have demonstrated mutualistic interactions between bacteria and B12 -dependent algae. Populations of the bacterium Mesorhizobium loti (B12 producer, carbon requirer) and the green alga Lobomonas rostrata (B12 requirer, carbon producer) in co-culture stabilise to an algae/bacteria ratio of 1/30, independent of initial inoculum ratio.

Here we consider the interactions between microbial populations separated in space. Experiments on hard agarose indicate that mutualistic interactions exist at a distance. We present a mathematical model capturing the essence of these experiments: growing populations of algae and bacteria coupled by a diffusive channel. Solutions to the model reveal rich dynamics. We will discuss these and speculate on the ecological significance of our findings for understanding environmental biofilms and microbial mats.

This discussion group aims to share research interests in Theoretical Biology and learn from each other in the form of weekly meetings. Contact Salvatore Tesoro (st590@cam.ac.uk) to be added to the BSDG mailing list and receive more information.

Biological and Statistical Physics Discussion Group (BSDG)

19th February 2015, TCM Seminar Room (530, Mott building), Cavendish Laboratory
Website

Lorenzo Di Michele will be talking about Ligand-mediated interactions between lipid vesicle: tuneable porosity and negative thermal expansion in lipid-DNA phases.

In the last decade DNA has become routinely used to drive the self-assembly of Brownian objects, including colloids an nanoparticles. In these systems, the particles are coated with DNA tethers, that bind to each other via selective and reversible Watson-Crick be pairing. Recently the same approach has been applied to more compliant units, including emulsion droplets and lipid vesicles. In these systems, the deformability of the substrates couples with the already complex statistical mechanics of multivalent interactions. Moreover, due to the liquid nature of the interfaces, DNA tethers can diffuse and rearrange, giving rise to nontrivial entropic contributions to the free energy. We recently investigated the emergent thermal response of systems of networks of DNA -functionalised lipid vesicles, leading to tuneable porosity and negative thermal expansion [Nature Communications 6:5948 2015]. I will discuss experimental findings and compare them with the predictions of a detailed analytical model. The results highlight the importance of entropic contributions to the coupling between the DNA tethers and the morphology of the substrates.

This discussion group aims to share research interests in Theoretical Biology and learn from each other in the form of weekly meetings. Contact Salvatore Tesoro (st590@cam.ac.uk) to be added to the BSDG mailing list and receive more information.

Biological and Statistical Physics Discussion Group (BSDG)

5th February 2015, TCM Seminar Room (530, Mott building), Cavendish Laboratory
Website

Professor Eugene Terentjev (Department of Physics) will be talking about Rotary molecular motors.

This discussion group aims to share research interests in Theoretical Biology and learn from each other in the form of weekly meetings. Contact Salvatore Tesoro (st590@cam.ac.uk) to be added to the BSDG mailing list and receive more information.

Biological and Statistical Physics Discussion Group (BSDG)

22nd January 2015, TCM Seminar Room (530, Mott building), Cavendish Laboratory
Website

Chris Forman (Department of Chemistry) will be talking about An energy landscape study highlighting the well engineered thermodynamics of collagen.

Can we design materials to handle energetic throughputs without disrupting their structure? Biology can. Indeed biology makes many complex materials which can inspire us to design materials with high performance that will improve our ability to manage the planet. Here I present a study of collagen using energy landscape techniques. I explain how the resulting model, with supporting data from NMR studies, suggest that collagen may be able to change conformation without a significant energy penalty. The resulting flexibility in conformation means that the equilibrium conformation across a particular range of temperatures is dominated by the entropy of the ring puckering system, resulting in thermal and mechanical stability. In effect, our study shows that collagen may be considered as an entropic spring and this has consequences in terms of heat dissipation of mechanical shocks. By discussing the thermodynamic properties of collagen I highlight how consideration of the molecular details of a material can have dramatic effects at the macroscopic levels. In turn, I briefly discuss how this may help us manage the deep relationship between global energy consumption and the manufacturing and molecular design of materials.

This discussion group aims to share research interests in Theoretical Biology and learn from each other in the form of weekly meetings. Contact Salvatore Tesoro (st590@cam.ac.uk) to be added to the BSDG mailing list and receive more information.

Biological and Statistical Physics Discussion Group (BSDG)

11th December 2014, TCM Seminar Room (530, Mott building), Cavendish Laboratory
Website

Sinisa Vukovic will be talking about Neurotransduction mechanism via GPCRs: alpha helix, the smallest spring in nature?.

A two part presentation demonstrates the use of computational methods in deciphering reaction mechanisms of protein-ligand interactions. The first part presents an example of a ligand as inhibitor. A statistical mechanical framework based on Inhomogeneous Fluid Solvation Theory is used to determine underlying mechanism of potency of an inhibitor toward a protein. The second part presents an example of a ligand as agonist. A mechanism of nerve signal transduction via GPC Rs is proposed. It is based on idea that a neurotransmitter interacts with not only residues of a protein but with its helical backbone structure. This interaction triggers a conformational change between 3-10 and 4-13 forms of the helix, in other words helix springs. Discussion on fundamentally opposing modes of mechanisms between ligands (inhibitors and agonists), as well as between proteins (enzymes and receptors, where one changes the ligand while the other changes itself), will close the talk.

This discussion group aims to share research interests in Theoretical Biology and learn from each other in the form of weekly meetings. Contact Salvatore Tesoro (st590@cam.ac.uk) to be added to the BSDG mailing list and receive more information.

First pub meeting of Theory of Living matter

November 26th at 6pm, The Boathouse, Chesterton Road, Cambridge

In our second pub meeting we will have two talks, a theoretical talk and an experimental talk. Both talks are intended to be understandable for a broad audience.

We will begin with a talk by John Biggins (Cavendish Laboratory) on The Mechanical Basis of Morphogenesis.

The development of an adult organism from a single cell requires complex shapes to emerge from simple ones. Such spontaneous shape formation is normally understood within Turing's reaction diffusion framework: chemical morphogens first set up spatial patterns then couple to growth to produce shapes. In this talk I will discuss a growing body of evidence that the shapes of biological organs are often sculpted directly by mechanical forces, without preliminary chemical patterning. In particular, I will discuss recent work on how the gut loops and how villi form, and some of my own results on the folding of the eye's ciliary muscle and the folding of the outer surface of the brain.

Then, after a short break, Amalia Joy Thompson (Department of Physiology) will talk about the Role of tissue stiffness in embryonic axon guidance.

Neuronal growth is essential for nervous system development and is also required for regeneration after nervous tissue injury. As axons and dendrites grow towards their targets, they are guided by environmental cues, including a well-characterised set of biochemical signals. Recent in vitro studies suggest that neuronal growth can also be regulated by mechanical properties of the substrate. However, the role of mechanical cues in axon pathfinding in vivo, and the spatiotemporal dynamics of tissue mechanics during early nervous system development, are still largely unknown. Here we investigate the role of tissue stiffness in axon guidance within the early embryo, using the Xenopus laevis optic tract as a model system. Retinal ganglion cell (RGC) axons form the optic tract by growing from the embryonic retina, along a stereotypical path on the brain surface, and terminating at their target, the tectum. We have developed in vivo atomic force microscopy (AFM) to map tissue stiffness along the optic tract at different developmental stages. We find that the embryonic brain is overall mechanically inhomogeneous, and that brain stiffness changes over time. Specifically, we find that the elastic stiffness of the tectum is consistently lower than the rest of the path taken by RGCs. Our results indicate that the path of RGCs is correlated with stiffness gradients in vivo, before axon growth stalls after reaching the softer region. These findings are consistent with a role for substrate mechanics in axon pathfinding, which might not only be crucial during development but also during regenerative processes in the nervous system.

After the talks there will be plenty of time for informal discussions. We will serve some snacks and there will be opportunities to order food and drinks.

More information and registration

Biological and Statistical Physics Discussion Group (BSDG)

6th November, 2014, TCM Seminar Room (530, Mott building), Cavendish Laboratory
Website

Pablo F. Damasceno (University of Michigan, Ann Arbor, Michigan, USA) will be talking about What the Bees Know and What They Don’t Know. Meanders on Shape, Packing and Self-Assembly in Nature.

Self-Assembly – the process by which building blocks achieve global order due solely to their local interactions with each other and the environment – is ubiquitous in Nature, from the magic ratio found in most rivers to the shape of viruses. Conceptually similar, packing problems – concerning the densest way of organizing shapes in a container – are also frequently found in Nature and have many connections to self-assembly. Departing from the historical question on “what gives honeycombs their shape”, I will cover the similarities and differences between packing and assembly and reveal how those concepts have been helping the development of new materials in the nano and colloidal scale.

This discussion group aims to share research interests in Theoretical Biology and learn from each other in the form of weekly meetings. Contact Salvatore Tesoro (st590@cam.ac.uk) to be added to the BSDG mailing list and receive more information.

Third regular meeting

October 28th from 6-8pm, Room LR3, Sainsbury Laboratory

The third regular meeting will start with a talk by Prof. Dennis Bray will give a talk on Protein computations and the origins of behaviour.

Cells are built up of molecular circuits that perform logical operations, analogous in many ways to electronic devices but with unique properties. Proteins in particular act like miniature transistors, controlling the biochemical processes of a cell and providing a basis for the sophisticated decision making of cells and organisms. I will illustrated these features with reference to the simple form of behaviour in which bacteria smell and swim towards distant sources of food. During bacterial chemotaxis, protein states encode the experiences of the cell past and present and use these data to select the best direction in which proceed—in effect to predict the future.

After the talk there will be plenty of time for informal discussions. We will serve some snacks and wine.

More information and registration

Biological and Statistical Physics Discussion Group (BSDG)

23rd October, 2014, TCM Seminar Room (530, Mott building), Cavendish Laboratory
Website

Emma Towlson (University of Cambridge) will be talking about The 'richness' of brain organisation: What a large-scale human brain functional network has in common with the C. elegans neuronal connectome and beginning to describe brain disorders in terms of disordered networks.

This discussion group aims to share research interests in Theoretical Biology and learn from each other in the form of weekly meetings. Contact Salvatore Tesoro (st590@cam.ac.uk) to be added to the BSDG mailing list and receive more information.

Biological and Statistical Physics Discussion Group (BSDG)

9th October, 2014, TCM Seminar Room (530, Mott building), Cavendish Laboratory
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Edouard Hannezo will be talking about A minimal theoretical model of epithelial shape.

We propose a minimal theoretical model of epithelial shape in 3D, based on cell adhesion and actomyosin contractility, which describes the various shapes of epithelial cells and the bending and buckling of epithelial sheets, as well as the relative stability of cellular tubes and spheres. We show that, to understand these processes, a full 3D description of the cells is needed, but that simple scaling laws can still be derived. The morphologies observed in vivo can be understood as stable points of mechanical equations and the transitions between them are either continuous or discontinuous. We then focus on epithelial sheet bending, a ubiquitous morphogenetic process. We calculate the curvature of an epithelium as a function of actin belt tension as well as of cell–cell and and cell–substrate tension.

Secondly, we incorporate in our model the stresses arising from cell division and death. When tissues grow in constrained environments, buckling instabilities are gener- ically expected, and we show that a simple biomechanical model can explain a wide variety of biological shapes, such as the intestinal wall or pathologies of biological tubes such as arteries and trachea.

We then apply these theories to the concrete example of the development of the Drosophila trachea, in collaboration with Bo Dong and Shigeo Hayashi (RIKEN Institute, Japan). Our findings demonstrate a mechanical role for the extracellular matrix and suggest that the interaction of the apical membrane and an elastic aECM determines the final morphology of biological tubes independent of cell shape.

This discussion group aims to share research interests in Theoretical Biology and learn from each other in the form of weekly meetings. Contact Salvatore Tesoro (st590@cam.ac.uk) to be added to the BSDG mailing list and receive more information.

First Tutorial

September 24th from 5-7pm, Room MR 15, Centre for Mathematical Sciences, Wilberforce Rd, Cambridge CB3 0WA

In this tutorial Philip Greulich and Steffen Rulands will give an Introduction to pattern formation. The lecture is intended to be understandable for a broad audience with an interest in and basic knowledge of mathematics. No preliminary knowledge in non linear dynamics or pattern formation will be required. However, participants are supposed to have basic training in mathematical methods, especially in dealing with differential equations.

To understand the formation of spatial patterns mathematical models combining nonlinear reactions and diffusion have been extensively studied. In his visionary work, Alan Turing investigated the stability of the simplest possible reaction-diffusion system which is capable of forming a pattern from a uniform state. In this lecture we will give an introduction to some elementary methods and simple models in the theory of pattern formation. The first part will deal with elementary definitions and the concept of linear stability, which will then be applied to derive Turing's mechanism. The second part will cover some more advanced pattern forming processes, such as wave propagation.

After the lecture we will have some wine and cookies and opportunity for discussions.

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First pub meeting of Theory of Living matter

July 30th at 6pm, The Brew House, 1 King St, CB1 1LH Cambridge

In this informal meeting we will have two talks, a theoretical talks and an experimental talk. Both talks are intended to be understandable for a broad audience. Henrik Boije (Department of Physiology, Development and Neuroscience) will give a talk on Building a retina: Extrinsic and intrinsic factors regulating cell fate in the developing retina.

We use the zebrafish retina as a model to understand how a pool of equipotent stem cells can create a complex organ of the correct size and cell type distribution. Analysis of cell lineages of retinal progenitor cells reveals a large variation in size and cell type composition suggesting an element of stochasticity during proliferation and cell fate assignment. However, stochasticity does not mean that these events are uncontrolled or random but rather that they operate according to defined probabilities creating statistically well-behaved ensembles. How environmental cues (extrinsic factors) and cell-autonomous decisions (intrinsic factors) regulate cell proliferation and differentiation remains elusive. We experimentally study intrinsic and extrinsic influences by combining cell transplantation with cell lineage tracing technologies. Our experiments reveal the fate changes that occur when the translation of key fate determinants is blocked by “morpholinos”. Based on these experiments and with knowledge of the transcriptional hierarchies during retina development we were able to develop a stochastic model, which takes into account the proliferative capacity and fate assignment of retinal progenitor cells.

Then, after a short break, Joel Peck (Department of Genetics) will talk about Is Life Impossible? Information, Sex, and the Origin of Complex Organisms.

Eigen’s Paradox is a logical puzzle concerned with the origin of complex life. It is presumed that, early in the history of life, mutation rates were much higher than they are in contemporary organisms. According to Manfred Eigen, this implies that the maximum amount of information that could have been stably encoded in the genomes of early organisms must have been severely limited. In contemporary organisms, the mechanisms of error prevention and correction are quite complex. This leads to a “chicken-and-egg problem.” How could life that is complex enough to allow the suppression of mutation to low levels have evolved while mutation rates were quite high? Eigen’s calculations are based on the idea that, if the genome with the best-possible fitness can not be maintained in a population, then “The information ... would slowly seep away until it is entirely lost.” However, this idea is not obviously based on any firm information-theoretic foundation. What really matters is whether, in a stable population, organisms are able to generate phenotypes that are complex enough to allow for highly effective error-prevention-and-correction mechanisms. This talk will present a re-analysis of the problem using this phenotypic-complexity criterion. The findings show that there are conditions where much more information can be stably encoded in the genome than would follow from Eigen’s criterion, despite the existence of relatively high mutation rates. The highest levels of information content are obtained when recombination occurs, and when each possible phenotype is produced by many different genotypes. The talk will also contain a few speculative comments about the possible role of information theory for other evolutionary problems, and in the life sciences in general.

After the talks there will be plenty of time for informal discussions. We will serve some snacks and there will be opportunities to order food and drinks.

More information and registration

Second regular meeting of Theory of Living Matter

June 25th from 6-8pm, Room LR3, Department of Engineering

Prof. Alfonso Martinez-Arias will give a talk on "Molecular dynamics and self organization in ensembles of mouse Embryonic Stem cells". We will then have a networking event with some wine and food.

A central question in developmental biology concerns the relationship between gene activity and the arrangements of cells that we call tissues and organs. Classical biology envisions this as the result of deterministic programmes of gene expression acting homogeneously within cell populations. However, analysis of gene expression at the level of single cells engaged in these programmes reveals an unexpected degree of transcriptional heterogeneity which needs to be reconciled with the homogeneous and reproducible organization observable at the level of large groups of cells. The mechanisms that mediate, maintain and regulate these heterogeneities are at the center of my interests and the main subject of the research of my group.

In this talk I shall discuss how we use mouse Embryonic Stem (ES) cells to understand the ways in which heterogeneous, and to a certain degree stochastic, patterns of gene expression are averaged within cell populations to produce dynamically stable patterns of cell fates in a reproducible manner. At the end I shall show some examples of symmetry breaking and self organization in ensembles of ES cells which raise significant challenges to both physicists and biologists.

Throughout my discussion I shall emphasize how statistical physics provides an inspiration and a reference to address the relationship between genes and tissues.

More information and registration

Roughly 50 participants made it to the somewhat hidden venue in the Department of Engineering. The inspirational talk by Prof. Martinez-Arias was followed by a lively speed-networking session.

Biological and Statistical Physics Discussion Group (BSDG)

June 12th at 12pm, TCM Seminar Room (530, Mott building), Cavendish Laboratory
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Otti Croze (BSS) will be talking about "Bacterial migration in porous media and the new biological statistical physics that describes it".

Many bacteria swim chemotactically: they navigate up chemical gradients. The biophysics of chemotaxis in liquids is well understood. Its study in porous media, however, has recently revealed unexpected surprises. Existing models describe chemotactic migration in porous media as if bacteria were gas particles in an external field. But this description, which maps onto ordinary statistical physics (with detailed balance), fails to describe the migration of E. coli bacteria in porous gels. A new transport theory, with chemotactic memory (and without detailed balance), is required to account for the observed suppression of chemotaxis in dense gels.

This finding has practical implications for attempts to use chemotactic bacteria to clean up soil (bioremediation). It is part of growing evidence that a new biological statistical physics needs to be developed to accurately describe populations of swimming, environment-sensing microorganisms. My talk will be in two parts. In the first (slides) I will motivate the topic, describe my experimental work on bacterial migration in agar gels and outline the theory. In the second (at the board) I will sketch the stat mech derivation of transport paramaters in porous media accounting for chemotactic memory.

An informal discussion session will follow and sandwiches will be offered. This discussion group aims to share research interests in Theoretical Biology and learn from each other in the form of weekly meetings. Contact Salvatore Tesoro (st590@cam.ac.uk) to be added to the BSDG mailing list and receive more information.

Biological and Statistical Physics Discussion Group (BSDG)

5th June, 2014, TCM Seminar Room (530, Mott building), Cavendish Laboratory
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Pietro Cicuta (BSS) will be talking about "The synchronised state of actively beating cilia: collective dynamical patterns emerge out of noise".

This discussion group aims to share research interests in Theoretical Biology and learn from each other in the form of weekly meetings. Contact Salvatore Tesoro (st590@cam.ac.uk) to be added to the BSDG mailing list and receive more information.

TLM introductory meeting

Wednesday, 28th May from 6-8pm in the Divinity School, opp. St. Johns college

We will briefly introduce the ideas and goals of this network. Prof. Ben Simons will then talk about a physicist's perspective on working in the life sciences, and present examples of how physical modelling approaches and theoretical work could change biological dogmas in stem cell research. Afterwards, a wine reception with canapes provides opportunities to get to know each other and to exchange perspectives.
More information and registration

With around 80 participants the introductory meeting turned out to be a great success. The large interest in the Theory of Living Matter group showed that there is a real need for a forum bringing theorists and experimentalists from different disciplines together. Thank you for all the positive feedback and the ideas on how this network should develop.

The TLM group organises regular meetings with high-profile speakers, informal pub meetings and tutorials for a broad scientific audience.