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Seminars (ICB)

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Event When Speaker Title
ICB 12th September 2001
15:30 to 17:30
HG Othmer Dicty Overview Tutorial
ICB 13th September 2001
15:30 to 17:30
Molecular motors Tutorial
ICB 14th September 2001
15:30 to 17:30
J Jaeger Developmental dynamics Tutorial
ICB 17th September 2001
15:30 to 17:30
Stochastic analysis Tutorial
ICB 18th September 2001
15:30 to 17:30
Developmental Biology Tutorial
ICB 19th September 2001
15:30 to 17:30
NP Smith Cardiac Physiology I Tutorial
ICB 20th September 2001
15:30 to 17:30
Cardiac Physiology II Tutorial
ICB 21st September 2001
15:30 to 17:30
Workshop prelim reports Tutorial
ICBW01 24th September 2001
13:30 to 13:40
Opening Remarks
ICBW01 24th September 2001
13:40 to 14:40
Modelling molecular events in a small volume of living cytoplasm
In a recent study, we proposed an atomic level structure for a lattice of chemotaxis receptors in coliform bacteria (Shimizu et al. Nature Cell Biol .2: 792-796, 2000). A unique feature of this model was that it created a small compartment between the plasma membrane and an extended hexagonal lattice of the signaling proteins CheA and CheW. The proposed compartment is 20-30 nm deep, perhaps 300-500 nm wide, and contains a thicket of extended coiled-coils forming the cytoplasmic domains of the chemotactic receptors. The compartment is not closed, and should be freely accessible to cytoplasmic proteins diffusing in from the lateral borders or through 10 nm diameter pores in the hexagonal lattice. Despite the absence of sealed boundaries, however, there is reason to think that this minute volume of bacterial cytoplasm will be highly enriched in two diffusible proteins, CheR and CheB, which are responsible for adaptation in the bacterial system. We are currently using computational methods to explore the possible movement of these enzymes through the "adaptation compartment". In particular we examined the possibility that these molecules might progress from receptor to receptor by swinging from one flexible region to another, like a monkey swinging through trees ("molecular brachiation"). We also attempted to predict temporal changes in protein conformation within such a molecular lattice. Could conformational changes in one receptor spread to neighboring receptors? If so, by what route and what will be the likely consequences for cellular behavior? Conclusions reached in this analysis are likely to lead to a clearer picture of the physiology of the chemotactic response in bacteria. They will also provide clues to the operation of other "privileged compartments" in both bacteria and eucaryotic cells.
ICBW01 24th September 2001
14:40 to 15:40
The role of the cytoskeleton in intracellular signalling
The cytoskeleton of eucaryotic cells represents an interconnected network of actin filaments, microtubulus and intemediate filaments, which extends over the entire cell. It has long been known that this network regulates cell motility, cell shape, gene expression and a number of other cell functions. Recently it has been recognized that mechanical forces may regulate intracellular signaling pathways and it has been suggested this may involve the cytoskeleton. On one hand the cytoskeleton provides docking sites for many signaling molecules, on the other hand, due to its interconnected character is capable to transmit mechanical signals between distinct parts of the cell. This dual role makes the cytoskeleton an ideal mechano-chemical conversion apparatus. The specific way, how the cytoskeleton may participate in intracellular signaling is not known. I will first show, using information from protein data basis and interaction networks that indeed there is a strong correlation between signaling molecules and cytoskeleton associated molecules. I will then present models for the specific mechanisms of the cytoskeleton's involvement in intracellular signal transduction.
ICBW01 24th September 2001
16:10 to 17:10
GATA-3 transcriptional memory in T helper lymphocytes a mathematical model of steady-state and temporal behaviour
T helper (Th) lymphocytes are central regulators of adaptive immune responses. Upon initial contact with antigen presenting cells, they differentiate into Th1 or Th2 cells. Th1 cells express activators of cellular immune responses such as IFN gamma, while Th2 cells stimulate humoral immune responses through the production of IL-4. The Th1/Th2 differentiation is determined by costimulatory cytokine signals acting on specific transcription factors. Recently, the transcription factor GATA-3 has been shown to induce the Th2 program of cytokine expression and to exhibit autoactivation of its expression. By means of a mathematical model of GATA-3 expression it is demonstrated how this autoregulatory loop can lead to an bistable switch between low and upregulated levels of GATA-3. On the basis of this mechanism, the establishment of a transcriptional memory for IL-4 expression through transient activation of the JAK/STAT6 pathway is analysed and compared with experimental results.
ICBW01 25th September 2001
09:20 to 09:30
Opening Remarks Meeting room 2 at Centre for Mathematical Sciences
ICBW01 25th September 2001
09:30 to 10:10
Reverse engineering of a developmental genetic regulatory network Meeting room 2 at the Centre for Mathematical Sciences
I will give an overview of a collaborative project with Prof. Eric Davidson (Caltech) in which we have been reverse engineering the genetic regulatory network underlying endoderm-mesoderm specification in sea urchin embryos.

To be able to carry out this work, we have developed - and are continuing to develop - a range of new software tools and an associated reverse engineering methodology which I will describe briefly.

ICBW01 25th September 2001
10:10 to 10:50
J Jäger Looking at the future of functional genomics from inside the Drosophila blastoderm -(Meeting Rm 2 at the Centre for Math. Sciences)
Functional genomics will ultimately involve the application of genomic methods to the full range of biological functions, including those that are properties of multicellular organisms. This includes areas such as neurobiology, development, macroevolution, and ecology. This talk will be concerned with the functional genomics of animal development. The central problem in animal development is the generation of body form. This problem was first considered by Aristotle, and in the nineteenth century is was shown that basic body form is determined by interactions among cells in a morphogenetic field. The determination of a morphogenetic field in development involves the expression of genes in spatial patterns. Spatially controlled gene expression cannot as yet be assayed in microarrays, but certain special properties of the fruit fly Drosophila which make it a premier system for developmental genetics also enable it to be used as a naturally grown differential display system for reverse engineering networks of genes. In this system we can approach fundamental scientific questions about development as well as certain computational questions that arise in the analysis of genomic level gene expression data.

Our approach is called the ``gene circuit method'', and it consists of 4 components: (1) The formulation of a theoretical model for gene regulation. (2) The acquisition of gene expression data using fluorescently tagged antibodies. (3) The determination of the values of parameters in the model or the demonstration that no such values exist by numerical fits to data. The results of (1), (2), and (3) are used (4) to validate the model by comparison to the existing experimental data and by making further predictions. Recent progress in all 4 of these areas will be discussed.

ICBW01 25th September 2001
11:10 to 11:50
G Von Dassow Models of modules: putting the molecular parts together into genetic devices (Meeting rm 2 at the Centre for Mathematical Sciences)
Our research into mathematical models of gene networks began with a curiosity about the genetic architecture of development: to what extent can we say that gene networks are modular building blocks of developmental mechanisms? By "module" we mean a small conspiracy of genes that together exhibit some functional behavior, intrinsic to the network itself and related to the functional role of that network in the organism. I emphasize that modularity is a working assumption, rather than something we are trying to prove rigorously. We've made an extended study of two such putative modules, the Drosophila segment polarity network, and the Drosophila neurogenic network. Our approach has been to do the computer-modeling equivalent of a biochemical reconstitution: add known facts to the model until it begins to exhibit life-like behaviors. The segment polarity module's job is to maintain boundaries; the neurogenic network's job is to mediate lateral inhibition; for both modules, minimal in silico reconstitutions exhibit those behaviors robustly with respect to the kinds of variation that we would expect genetic networks to experience in real life. I'll discuss a handful of results from these models that we find provocative: first, I'll discuss what we've learned about what makes these modules' functional behaviors robust to parameter variation and other insults, and how we think these models shed light on the phenomenon of canalization; next, I'll describe some instances in which the failure of the segment polarity models to account for certain details led us to mechanistic questions about the real network; and finally, I'll talk about some ideas, stimulated by the models, about how these two networks arose, highlighting the hierarchical, nested nature of gene networks.
Copyright © Isaac Newton Institute
ICBW01 25th September 2001
11:50 to 12:30
Microarrays and yeast: insights into gene regulation Meeting room 2 at the Centre for Mathematical Sciences
ICBW01 25th September 2001
13:50 to 14:00
K Vass Normalisation and local variation in microarrays Meeting room 2 at Centre for Mathematical Sciences
ICBW01 25th September 2001
14:00 to 14:40
A Brazma Reconstructing elements of gene networks from genome scale microarray data (Meeting rm 2 at the Centre for Mathematical Sciences)
ICBW01 25th September 2001
14:40 to 15:20
From gene expression to gene interaction Meeting room 2 at the Centre for Mathematical Sciences
ICBW01 25th September 2001
15:40 to 16:20
O Wolkenhauer System theoretic models of gene expression and gene interactions Meeting room 2 at the Centre for Mathematical Sciences
ICBW01 25th September 2001
16:20 to 16:45
Funding opportunities in bioinformatics and theoretical biology Meeting room 2 at the Centre for Mathematical Sciences
ICBW01 25th September 2001
16:45 to 17:20
Discussion Session Meeting room 2 at The Centre for Mathematical Sciences
ICBW01 26th September 2001
10:00 to 11:00
J Lewis Notch signalling in spatial and temporal patterning
ICBW01 26th September 2001
11:30 to 12:30
Extracellular matrix alignment by cells: discrete and continuous models compared
The basic event in the formation of scar tissue in a wound is the remodelling of extracellular matrix by fibroblasts cells. These cells enter the wound from surrounding tissue, break down the fibrin-based blood clot, and replace it with a collagen-based matrix. The orientation of the new collagen fibres involves a complex interplay between cells and matrix: cells tend to move along collagen fibres, and also reorient fibres towards their direction of movement. I will discuss and compare two different approaches to modelling this process of fibre reorientation by fibroblasts. I will describe a discrete formulation in which each cell is represented as a separate entity, within a continuum of collagen fibres. I will compare this with a continuous model with densities of cells and matrix that are functions of space and orientation. The two approaches offer different insights into the process of matrix alignment and I will discuss their implications for scar tissue formation.
ICBW01 26th September 2001
14:30 to 15:30
In vivo imaging as a bridge between molecular, cellular and tissue level data in embryonic vertebrate development
One of the beautiful aspects of embryonic developmental is the sculpting of cells and tissue into functioning structures. Although the recent explosion of molecular data has provided tremendous insight into the machinery underlying the sculpting processes, it is a major challenge to coordinate molecular and cellular data in dynamic systems. The next steps of determining the function of genes will rely on our ability to create a framework to visualize and analyze cell movements, cell signaling and gene expression in living systems in 2 and 3 dimensions. To approach this, we are using in vivo imaging as a bridge between the levels of the biology and between experiment and theoretical modeling. We have developed techniques to trace and analyze fluorescently labeled cell movements and study cell signaling dynamically in living chick and mouse embryos. To more accurately coordinate gene expression patterns with morphological changes, we use time-lapse imaging to pinpoint the location of cells at critical times during a process before fixing the embryo and comparing the pattern of gene expression to cell positions. An excellent model system to study the interaction of rapid changes in gene expression and morphology is the segmentation of tissue into somites and we will present data from our studies in chick. We will also present work from a new project investigating blood formation and cardiovascular development in mouse.
ICBW01 26th September 2001
16:00 to 17:00
Intracellular calicum cycling and control of action potential duration
Cardiac electrophysiology is a field with a rich history of integrative modeling. A particularly important milestone was the development of the first biophysically-based cell model describing interactions between voltage-gated membrane currents, pumps and exchangers, and intracellular calcium (Ca2+) cycling processes (DiFrancesco & Noble, Phil. Trans. Roy. Soc. Lond. B 307: 353), and the subsequent elaboration of this model to describe the cardiac ventricular myocyte action potential (Noble et al. Ann. N.Y. Acad. Sci. 639: 334; Luo, C-H and Rudy, Y. Circ. Res.74: 1071). These, and all other integrative models of the myocyte developed to date are of a type known as "common pool" models (Stern, Biophys. J. 63: 497). In such models, Ca2+ flux through L-type Ca2+ channels (LCCs) and ryanodine sensitive Ca2+ release channels (RyRs) in the junctional sarcoplasmic reticulum (JSR) membrane is directed into a common Ca2+ compartment. Ca2+ within this common pool also serves as activator Ca2+ triggering JSR Ca2+ release. In a modeling tour de force, Stern demonstrated that common pool models are structurally unstable, exhibiting all-or-none Ca2+ release except (possibly) over some narrow range of model parameters. Despite this inability to reproduce experimentally measured properties of graded JSR Ca2+ release, common pool models have been very successful in reproducing and predicting a range of myocyte behaviors. This includes properties of interval-force relationships that depend heavily on intracellular Ca2+ uptake and release mechanisms (Rice et al. Am. J. Physiol. 278: H913). Given these findings, one may wonder whether or not it is important to incorporate an accurate biophysical description of graded JSR Ca2+ release in computational models of the cardiac myocyte.

Stern went on to propose the "local-control" theory of Ca2+ release. In this theory, individual LCCs, the set of RyR with which they communicate, and the subspace within which they communicate, defines a functional release unit (FRU). Local control theory holds that while Ca2+ release within each FRU may be all or none, the averaged behavior of many independent FRUs reflects the probability of opening of LCCs. We have previously developed a model of the functional release unit (FRU) consisting of one LCC, eight RyR, and the volume in which they are enclosed (Biophys J 77:1871-84). To study the impact of local Ca2+ control in the context of the whole cell AP, we have developed a new class of ventricular cell model which combines the stochastic simulation of a large number of independent FRUs with the solution of a system of coupled ordinary differential equations describing the full complement of card

ICBW01 27th September 2001
10:00 to 11:00
Mechanisms, variation, conservation, and integration of early morphogenic machanies in vertebrates
Investigation of the mechanism and morphogenic function of convergence, extension, and ingression of cells in the early morphogenesis of several species of amphibians shows that similar morphogenic movements are driven by different cell behaviors and similar cell behaviors have different morphogenic consequences, depending on how the behaviors are integrated in the larger context. Convergence and extension of the axial mesoderm, the paraxial mesoderm and the neural plate play major roles in gastrulation, neurulation, and body axis formation in amphibians, and probably in other vertebrates as well. Convergent extension of both mesodermal and neural tissues in the anuran (tail-less amphibian), Xenopus laevis, share the feature of occurring by mediolateral intercalation of an initially short and wide array of cells to produce a longer, narrower array. These tissues differ in that intercalation of mesodermal cells is driven by a bipolar, mediolaterally oriented protrusive activity whereas intercalation of neural cells is driven by a medially directed, monopolar protrusive activity. They also differ in that the normal, monopolar mode of neural cell intercalation is dependent on the midline tissues of notoplate or notochord, whereas no midline is defined in the bipolar mode of mesodermal cell intercalation. Despite their differences, the biomechanical integration of these local cell intercalation behaviors is similar in the two tissues- a pushing force is exerted in the anterior-posterior axis and tension is exerted in the transverse, mediolateral axis. The result of the pushing forces result in extension of both the mesoderm and neural tissue in the anterior-posterior axis. The mesoderm stiffens in the anterior-posterior axis during extension, thus increasing its resistance to buckling. In contrast, the consequence of the transverse tension generated by convergence is context dependent and differs between neural and mesodermal tissues. The lateral edges of the neural plate are free to move to the midline as the attached, lateral epidermis spreads, allowing neural fold fusion and neural tube closure. In the mesodermal tissue, however, the lateral edges are attached to the contracting vegetal endoderm. As a result, convergence generates hoop stress across the dorsal lip, which pulls the dorsal midline ventrally, thus aiding and abetting involution and blastopore closure. Thus similar cell behaviors produce dramatically different morphogenic results, dependent on their context.
ICBW01 27th September 2001
11:30 to 12:30
Cell movements during early zebrafish morphogenesis
The development of the vertebrate embryo depends upon substantial cell rearrangement to shape an amorphous ball of cells into an animal. We know in general terms from fate mapping studies where cells will go during this process but in many cases we know little about the actual forces and movements involved. We are looking at these problems using the zebrafish as a model organism. The zebrafish has many advantageous qualities for these studies, notably it grows rapidly with a transparent embryo in which all cells can be visualised. There also exist many mutant lines deficient in aspects of morphogenesis. We have developed methods of following and analysing the movements of many hundreds of cells in the early zebrafish embryo. The philosophy of our approach is that if we can trace the movements all the cells within a significant volume of the embryo we can begin to ask questions about the cellular mechanisms that cause the tissue to change shape. Our analyses allow us to generate metrics that can be used to describe changes in behaviours in time and in space and to compare events inmutant embryos to those in the wild type. In this way we have begun to isolate the component mechanisms that are involved in the earliest stages of gastrulation. I will present two stages in this process, the organisation of the blastoderm into germ layers, and the subsequent convergence and extension of the axial mesoderm. In both cases, we compare the patterns of cell reorganisation in wild type and mutant animals and from this try to infer the underlying mechanisms.
ICBW01 27th September 2001
14:30 to 15:30
K Weijer The control of cell movement during Dictyostelium morphogenesis
Starvation results in the chemotactic aggregation of single cells of the social amoebae Dictyostelium discoideum to form a fruiting body. Morphogenesis results from the coordinated movement of differentiating cells. We study the dynamics and geometry signals controlling cell movement during all stages of development. Cell movement is controlled by propagating waves of the chemoattractant cAMP. During aggregation these waves have the form of target patterns or simple spirals. In the mound and slug stage of development the waves have more complex geometry's, such as multi-armed scroll waves. We can now visualise cAMP signal transduction at the single cell level in vivo and are analysing the dynamics of cAMP signalling in all celltypes during development in a series of signalling and movement mutants. We correlate the signalling and movement response of individual cells and begin to understand how the geometry of the waves in conjunction with a celltype specific differential chemotactic movement gives rise to the organism's characteristic morphogenesis. We have formalised these findings into both discrete and continuous mathematical models that can describe the aggregation, mound and slug stages of Dictyostelium development.
ICBW01 27th September 2001
16:00 to 17:00
P Hunter Physiome Projects: The heart, lungs and musculo-skeletal system
The IUPS Physiome Project uses anatomically and biophysically based computational modelling to analyse physiological function in terms of underlying structure, material properties and molecular mechanisms. Markup languages are being defined for describing cell, tissue and organ structure, material properties and physiological function. This talk will outline the development of these markup languages and their associated software tools and describe the development of Physiome models for the heart, lungs and musculo-skeletal system.
ICBW01 28th September 2001
09:00 to 10:00
ATP-sensitive K-channels and insulin secretion in health and disease
ATP sensitive K-channels (ATP channels) play important roles in a diverse range of tissues (including pancreatic beta-cells, neurones, and cardiac, skeletal and smooth muscles) by coupling the metabolic state of the cell to its electrical activity. In pancreatic beta-cells, for example, K ATP closure in response to glucose metabolism produces membrane depolarization, leading to Ca 2+ influx and insulin secretion. K ATP channels are also involved in glucose sensing in hypothalamic neurones, in ischemic preconditioning of cardiac muscle and, in vascular smooth muscle, in the regulation of vessel tone. Metabolic regulation is mediated by changes in intracellular ATP (which blocks the channel) and MgADP (which activates the channel). K ATP channels are inhibited by sulphonylurea drugs, which stimulate insulin secretion and are used to treat type 2 diabetes, and activated by K ATP-channel openers, a structurally diverse group of drugs with a wide range of potential therapeutic applications.

K ATP channels share a common pore-forming subunit, Kir6.2, which associates in a 4:4 heteromeric complex with different sulphonylurea receptor isoforms (SUR1 in beta-cells, SUR2A in heart, and SUR2B in smooth muscle). Kir6.2 serves as an ATP-sensitive pore while SUR acts as a regulatory subunit, endowing the channel with sensitivity to the stimulatory effects of MgADP and K ATP-channel openers and the inhibitory action of sulphonylureas. K ATP channels containing different types of SUR subunit show different sensitivities to sulphonylureas and K ATP-channel openers. Mutations in SUR1 or Kir6.2 that result in channel closure produce congenital hypoglycaemia of infancy in man, a disease of excessive insulin secretion. Conversely, impaired cell metabolism, or mutations in Kir6.2, which lead to enhanced channel activity, result in diabetes.

This talk will present an overview of our currents studies on the relationship between K ATP-channel structure and function, focusing on three main topics: inhibition by ATP; activation by Mg-nucleotides such as MgADP and MgATP; and the role of K ATP channels in disease.

ICBW01 28th September 2001
10:00 to 11:00
D Noble From genes to whole organs: vertical integration using mathematical simulation of the heart
Biological modelling of cells, organs and systems has reached a very significant stage of development. Particularly at the cellular level, there has been a long period of iteration between simulation and experiment (Noble & Rudy, 2001). We have therefore achieved the levels of detail and accuracy that are required for the effective use of models in drug development. To be useful in this way, biological models must reach down to the level of proteins (receptors, transporters, enzymes etc), yet they must also reconstruct functionality right up to the levels of organs and systems. This is now possible and three important developments have made it so:
  • Relevant molecular and biophysical data on many proteins and the genes that code for them is now available. This is particularly true for ion transporters (Ashcroft, 2000) The complexity of the biological processes that can now be modelled is such that valuable counter-intuitive predictions are emerging (Noble & Colatsky, 2000). Multiple target identification is also possible.
  • Computer power has increased to meet the demands. Even very complex cell models involving up to 50 different protein functions can be run on single processor machines, while parallel computers are now powerful enough to enable whole organ modelling to be achieved. (Kohl et al 2000)

    I will illustrate these points with reference to models of the heart.

    The criterion that models must reach down to the level of proteins automatically guarantees that they will also reach down to the level of gene mutations when these are reflected in identifiable changes in protein function (Noble 2001). Changes in expression levels characteristic of disease states can also be represented. These developments ensure that it will be possible to use simulation as an essential aid to patient stratification. I will illustrate these points with reference to sodium channel mutations.

  • ICBW01 28th September 2001
    11:30 to 12:30
    Closing discussion and closing remarks
    ICB 1st October 2001
    09:00 to 10:00
    Tutorial on developmental mechanics
    ICB 1st October 2001
    10:30 to 11:30
    Mechanics in plant morphogenesis
    ICB 1st October 2001
    14:00 to 15:00
    P Hunter Tutorial on cardiac mechanics
    ICB 2nd October 2001
    11:30 to 12:30
    Fundamentals of solid mechanics
    ICB 3rd October 2001
    15:30 to 16:30
    Tutorial on developmental mechanics
    ICB 4th October 2001
    14:30 to 15:30
    PP Ponte Castaneda Tutorial on homogenisation
    ICB 9th October 2001
    14:00 to 15:00
    Electrical wave propagation in the heart: dynamics of scroll waves in anisotropic excitable media
    ICB 11th October 2001
    13:30 to 14:30
    S Grand Computational models you can cuddle
    Despite a lingering 'physics envy', most biologists now recognise that cells, organs, organisms and ecosystems are simply too non-linear to be reducible to their parts alone and need to be understood as the totality of the relationships between those parts. As a consequence, analysis is increasingly being supplemented by synthesis in the form of computer models. Nevertheless, a requirement for biological veracity, and the complexity and detail that this implies, can sometime make it hard to see the wood for all the trees.
    One way to separate the general from the specific, and hence hope to discover some of the abstract organisational and self-organisational principles that underlie biological systems, is to start instead with a blank sheet and a pile of biologically plausible building blocks, and attempt to build a complete working organism (albeit a relatively simple one) from scratch.
    Ten years ago I set myself such a goal, under the cunning disguise of writing a computer game. From a heap of 'genes', 'neurons', 'chemicals' and 'receptors' I constructed a species of artifical creatures that could learn, behave, interact, reproduce and evolve. Today I'm building a robot creature with the goal of understanding some of the general principles underlying the mammalian brain. Whether these toy creatures tell us much about real biology is questionable, but they are certainly some of the most complex and complete computational models of organisms yet attempted, and I hope you may be interested in hearing about the things I learned from building them.
    ICB 15th October 2001
    15:30 to 16:30
    PP Ponte Castaneda Tutorial on homogenisation (part 2)
    ICB 16th October 2001
    14:00 to 15:00
    Modelling limb outgrowth and gene expression in vertebrates
    ICB 17th October 2001
    13:30 to 14:30
    Towards a quantative single-cell-based model approach to multicellular systems: early developmental stages and tumour spheriods
    ICB 18th October 2001
    14:00 to 14:45
    E Cytrynbaum Stability of the travelling pulse and the restitution hypothesis
    ICB 18th October 2001
    14:45 to 15:30
    Stochastic transitions between fixed points
    ICB 22nd October 2001
    15:30 to 16:30
    E Geigant Bifurcation analysis of an orientational aggregation model
    ICB 23rd October 2001
    11:00 to 13:00
    Discussion group on computational cardiology
    ICB 23rd October 2001
    13:30 to 14:15
    Molecular evolution of brain tumours
    ICB 23rd October 2001
    14:15 to 15:30
    Growth, curvature and pattern formation
    ICB 29th October 2001
    14:00 to 16:30
    Welcome discussion
    ICB 30th October 2001
    14:00 to 15:00
    Modelling the molecular mechanism of sex determination in Drosophila melanogaster
    ICB 31st October 2001
    14:00 to 15:00
    Informal talks
    ICB 1st November 2001
    14:00 to 17:00
    TBA
    ICB 2nd November 2001
    14:00 to 15:00
    Informal talks
    ICB 5th November 2001
    14:00 to 15:30
    Immunology workshop
    ICB 6th November 2001
    14:00 to 15:00
    Epidemiology tutorial
    ICB 9th November 2001
    14:00 to 15:30
    Ecology workshop
    ICB 12th November 2001
    14:00 to 15:00
    Immunology workshop
    ICB 12th November 2001
    15:00 to 17:00
    Epidemiology workshop
    ICB 13th November 2001
    14:00 to 15:00
    N Barton Genetic relationships in a spatially continuous population
    ICB 15th November 2001
    14:00 to 15:00
    Sex causes altruism
    ICB 16th November 2001
    14:00 to 16:00
    Cell-cell interactions and signalling in immunology
    ICB 20th November 2001
    10:00 to 11:00
    ICB organisers meeting
    ICB 20th November 2001
    14:00 to 16:00
    V Capasso Tutorial on stochastic modelling
    ICB 21st November 2001
    13:30 to 14:30
    Modeling pattern formation in interacting cell systems with cellular automata
    ICB 21st November 2001
    14:00 to 16:00
    Ecology workshop
    ICB 22nd November 2001
    14:00 to 15:00
    Continuum-discrete models of tumour-induced angiogenesis and invasion
    ICB 26th November 2001
    14:00 to 15:00
    Tutorial: The organisation of insect societies
    ICB 27th November 2001
    11:00 to 17:30
    Theoretical immunology discussion
    ICB 27th November 2001
    11:30 to 13:00
    Epidemiology workshop
    ICB 27th November 2001
    14:00 to 15:00
    Organisation of complex systems: social foraging
    ICB 28th November 2001
    13:30 to 14:30
    From individual to population models in chemotaxis
    ICB 29th November 2001
    14:00 to 15:00
    M Reuter The evolution of co-operation and conflict
    ICBW02 3rd December 2001
    09:00 to 09:50
    Patchiness in excitable systems with shear flows
    ICBW02 3rd December 2001
    09:50 to 10:15
    Foraging strategies for patchy environments
    ICBW02 3rd December 2001
    10:15 to 10:40
    Pattern formation in models of plankton-fish dynamics in a patchy and noisy environment
    ICBW02 3rd December 2001
    11:10 to 11:35
    Plankton blooms in chaotic flows
    ICBW02 3rd December 2001
    11:35 to 12:00
    Chaos and order in plankton spatio-temporal dynamics
    ICBW02 3rd December 2001
    13:30 to 13:55
    Non-stationary bacterial population wave propagation
    ICBW02 3rd December 2001
    13:55 to 14:20
    Latest advances in modelling spatio-temporal pattern formation in plankton communities
    ICB 3rd December 2001
    14:00 to 15:00
    Epidemiology working group
    ICBW02 3rd December 2001
    14:20 to 14:45
    Travelling waves in a simple PZ model
    ICBW02 3rd December 2001
    14:45 to 15:10
    Dynamics of group formation in collective motion of organisms
    ICBW02 3rd December 2001
    15:50 to 16:40
    The control of differential chemotactic cell movement during dictyostelium morphogenesis
    ICBW02 3rd December 2001
    16:40 to 17:05
    Cellular slime mold modelled with discrete viscoelastic cells
    ICBW02 3rd December 2001
    17:05 to 17:30
    Travelling pulse patterns in chemotactic species
    ICBW02 4th December 2001
    09:00 to 09:50
    J Kessler Individual and collective dynamics of swimming micro-organisms
    ICBW02 4th December 2001
    09:50 to 10:15
    A Swift-Hohenberg model for bioconvection
    ICBW02 4th December 2001
    10:15 to 10:40
    Alga motility measured by laser tracking method
    ICBW02 4th December 2001
    11:20 to 11:45
    Plumes in bacterial bioconvection
    ICBW02 4th December 2001
    11:45 to 12:10
    Mixing and feeding processes in choanoflagellates
    ICBW02 4th December 2001
    12:10 to 12:35
    A Roberts Is an intracellular gravity receptor required to explain gravitaxis in swimming micro-organisms?
    ICBW02 4th December 2001
    14:00 to 14:25
    A Manela & I Frankel Generalised Taylor dispersion in sheared suspensions of swimming micro-organisms
    ICB 4th December 2001
    14:00 to 16:00
    Social insects working group: discussion of robustness
    ICBW02 4th December 2001
    14:25 to 14:50
    In situ measurement of the diurnal phototactic behaviour of phototrophic bacteria in a lake
    ICBW02 4th December 2001
    14:50 to 15:15
    Janosi Bioconvection and bacterial ecology
    ICBW02 4th December 2001
    15:45 to 16:10
    Phototactic bioconvection in two dimensions
    ICBW02 4th December 2001
    16:10 to 16:35
    Pattern formation in higher organisms: mechanistic models of carnivore home range patterns
    ICBW02 4th December 2001
    16:35 to 17:00
    Growth, curvature and patterns
    ICBW02 5th December 2001
    09:00 to 09:50
    Cell signalling and transduction in angiogenesis: a "simple" model for the MAP kinase cascade in endothelial cells
    ICBW02 5th December 2001
    09:50 to 10:15
    KJ Painter From local models of signalling to macroscopic modelling of movement
    ICBW02 5th December 2001
    10:15 to 10:40
    M Holmes A simple mathematical model of cellular motion exhibiting chemotaxis
    ICBW02 5th December 2001
    11:10 to 11:35
    Primitive streak initiation in early development
    ICBW02 5th December 2001
    11:35 to 12:00
    The interplay of angiogenic signals during capillary formation
    ICBW02 5th December 2001
    12:00 to 12:25
    Tumour angiogenesis and the action of angiostatins
    ICBW02 5th December 2001
    14:00 to 14:50
    Pattern formation due to reproduction and movement of bacterial cells- experiments and modelling
    ICB 5th December 2001
    14:00 to 15:00
    W Foster Soldier aphids - the evolution of co-operation in a clonal animal
    ICBW02 5th December 2001
    14:50 to 15:15
    M Bees Bacterial swarming and thin-film flow in colonies of Serratia liquefacians
    ICBW02 5th December 2001
    15:15 to 15:40
    HG Othmer Macroscopic behaviour from microscopic rules in bacteria
    ICBW02 5th December 2001
    16:10 to 16:35
    R Satnoianu Bacterial chemotaxis: from the behavioural response to stepwise changes in temporal signals
    ICBW02 5th December 2001
    16:35 to 17:00
    NJ Burroughs Spatial dynamic of an amoeba-bacterial ecology
    ICB 6th December 2001
    14:00 to 15:00
    N Ferguson Spatiotemporal spread of the GB foot and mouth disease epidemic and implications for control
    ICB 6th December 2001
    16:00 to 17:30
    Social insects working group: discussion of robustness
    ICBW03 7th December 2001
    10:00 to 11:00
    N Franks From simple rules of thumb to collective intelligence
    ICBW03 7th December 2001
    11:30 to 12:30
    Some aspects of morphogenesis in social insects
    ICBW03 7th December 2001
    14:00 to 14:30
    From individual to collective behaviour in nest site selection by the ant Leptothorax albipennis
    ICBW03 7th December 2001
    14:30 to 14:50
    Automated observation and modelling of social insect colonies
    ICBW03 7th December 2001
    14:50 to 15:10
    A graphic computer model which generates realistic brood patterns found in social hornet (Vespa) colonies despite using simple rules
    ICBW03 7th December 2001
    15:10 to 15:30
    Nest's morphongenesis resulting from fingering
    ICBW03 7th December 2001
    16:30 to 17:30
    W Tschinkel Ant nest architecture: a record of collective action
    ICBW03 8th December 2001
    09:00 to 10:00
    Do social insects self-organise?
    ICBW03 8th December 2001
    10:00 to 10:20
    M Myerscough Are individual differences important in colony-wide organisation in honey bees
    ICBW03 8th December 2001
    10:20 to 10:42
    Multilevel organisation of insect societies: the need to identify and model the organs and tissues of superorganisms
    ICBW03 8th December 2001
    10:40 to 11:00
    A Sendova-Franks Random walk models of worker sorting in ant colonies
    ICBW03 8th December 2001
    11:30 to 12:00
    Small-scale vegetation patterns, individual behaviour and swarm formation in the desert locuts
    ICBW03 8th December 2001
    12:00 to 12:20
    Gregariousness and the division of labour in ant societies
    ICBW03 8th December 2001
    12:20 to 12:40
    Colony size, polydomy, production and the division of labour in colonies of the ant Leptothorax albipennis
    ICBW03 8th December 2001
    12:40 to 13:00
    Clean bees: modelling hygenic behaviour in honey bees
    ICBW03 8th December 2001
    14:00 to 15:00
    Choosing a new home: how the scouts in a honey bee swarm make a unanimous decision
    ICBW03 8th December 2001
    15:30 to 16:00
    Ant colony optimization for difficult optimization problems
    ICBW03 8th December 2001
    16:00 to 16:20
    Collective optimization: the artificial ants way
    ICBW03 8th December 2001
    16:20 to 16:40
    The organisation of traffic on army ant trails
    ICBW03 8th December 2001
    16:40 to 17:00
    F Saffre ``Anelosimus artificius" a virtual social spider to swarm the World- Wide-Web?
    ICBW03 8th December 2001
    17:00 to 17:15
    Closing remarks
    ICBW04 10th December 2001
    10:00 to 11:00
    Appropriate macroscopic behaviour of the immune system, from distributed microscopic feedback
    Arguments are given for the tenet that the immune system can usefully be regarded as having short term goals -- which typically overlap and are often contradictory. Diverse sensors can measure how far the system is from its various goals. Simple models illustrate how distributed feedbacks based on sensory information can (i) harmonize conflicting goals, (ii) improve the performance of a given type of effector cell, (iii) cause the preferential amplification of more potent effectors.
    ICBW04 10th December 2001
    11:30 to 12:30
    Treatment strategies against immuno-suppressive diseases
    ICBW04 10th December 2001
    14:30 to 15:30
    S Bonhoeffer The times' tables of viral resistance
    Simple population biological models have been instrumental in uncovering the highly dynamic nature of HIV replication in infected patients. These models can be extended to study the dynamics of the evolution of drug resistance in treated individuals. In my talk I will first give an introduction into the basics of these models. I will then discuss some general properties of virus resistance models and put them into the context of relevant biological data. I will apply quasispecies theory to virus dynamical models to investigate the mutation-selection process and its consequences for viral diversity before and during therapy. Finally I will discuss how fitness differences between competing viral variants can be estimated reliably from experimental data.
    ICBW04 10th December 2001
    16:00 to 17:00
    RN Antia Modeling CD8 Memory
    The generation and maintenance of immunological memory is a central problem in immunology. In this talk we address the following aspects of this problem focusing on CD8 responses.
    1. Generation of memory: Recent experimental results show that brief stimulation with antigen is sufficient to cause antigen-specific CD8 cells to undergo sustained proliferation followed by differentiation into memory cells. We use simple mathematical models determine the characteristics of both the antigen-dependent and the antigen-independent components of the response in order that they are consistent with existing data on the dynamics of CD8 responses.

    2. The memory phase: We use simple models to show how the longevity of immune memory depends critically on the mechanism for maintenance of homeostasis of CD8 cell populations. We We examine the dynamics of protection following re-stimulation with pathogens. Specifically we determine the regulation of secondary responses and the conditions under which memory is sufficient to give rise to protection.

    ICBW04 11th December 2001
    09:00 to 10:00
    A Hastings The dependence of the design of marine reserve networks on dispersal behaviour
    I will describe how the design of marine reserve networks depends on different descriptions of dispersal, focussing on designs based on fishing concerns and on sustatinability. The mathematical tools will be developed from integro-difference equations, and the sensivity and robustness of results to changes in the underlying assumptions will be emphasized.
    ICBW04 11th December 2001
    10:00 to 11:00
    HCJ Godfray Age-structured models of insect natural-enemy interactions
    ICBW04 11th December 2001
    11:30 to 12:30
    MA Lewis Territorial pattern formation through scent marking
    Social carnivores, such as wolves and coyotes, have distinct and well-defined home ranges. During the formation of these home ranges scent marks provide important cues regarding the use of space by familiar and foreign packs. In this talk I will propose a mechanism for territorial pattern formation through interactions with familiar scent marks. Rules for the behavior of individuals are translated to a partial differential equation (PDE) model. Analysis of this PDE model, through use application an `energy method', shows the formation of distinct territories with abrupt edges. Connections will be made to earlier ecological models for aggregating populations (eg. Turchin 1989, Journal of Animal Ecology (58): 75-100).


    The mechanism proposed here differs from previous models for territorial pattern formation which have required a den site as the organizational center around which the territory is formed. Thus the model explains field observations of well-defined home ranges in the absence of den sites, and even in the absence of surrounding packs.

    ICBW04 11th December 2001
    14:30 to 15:30
    Masting of forest trees - intermittent and synchronised
    1. Many trees in mature forests, including beaches and oaks, show intermittent reproduction (masting). Intensive flowering and seed production occur only once in several years, often synchronized over a long distance. The reserve of a tree is affected by the flowering activity of other individuals in the same forest because successful fruit production requires pollen produced by other individuals. We study a coupled map model for the dynamics of energy reserve of individuals: a single tree grows in each site of a 2-dimensional finite lattice.
    2. Without pollen limitation, trees in the forest show independent chaotic fluctuation. Coupling of trees via pollen exchange results in reproduction being synchronized partially or completely over the forest. When the coupling is global, we find perfectly synchronized periodic reproduction, synchronized reproduction with a chaotic time series, clustering phenomena, and chaotic reproduction of trees without synchronization over individuals. There are many parameter windows in which synchronized reproduction of trees show a stable periodic fluctuation. For perfectly synchronized forests, we can calculate all the Lyapunov exponents analytically. They shows that synchronized reproduction of trees can occur only if trees flower at low (but positive) levels in a significant fraction of years, resulting in small fruit sets due to the shortage of outcross pollen.
    3. Next, we study a coupled map lattice in which the pollen availability for a tree is the average flowering intensity within its local neighborhood. Analysis of dynamic spatial covariance shows that strong synchronization of tree reproduction can develop over the whole forest that may be orders of magnitude larger than the distance of direct pollen exchange between trees. The fluctuation is close to a cycle of period 2. In addition, non-uniform spatial patterns are generated, but the enhanced spatial covariance caused by the spatial heterogeneity is restricted to a short range, only a few times larger than the spatial range of direct interaction. When pollen exchange occurs beyond the nearest neighbors, the local spatial pattern becomes proportionalily larger but the condition for synchronization of the whole forest and its magnitude are the same as the case with the nearest neighbor pollen exchange. When a fraction of seeds are sired by globally dispersed pollen and the rest are by local pollen, the long-range synchronization can occur for a wide parameter region, and trees may engage in a fluctuation with masting interval longer than 2.
    ICBW04 12th December 2001
    10:00 to 11:00
    Extensive MHC polymorphism requires frequency-dependent selection by coevolving pathogens
    There are ample examples of pathogens adapting towards evasion of immune responses. A well-known example commonly thought to reflect adaptation of hosts to pathogens is the polymorphism of major histocompatibility (MHC) molecules. MHC molecules play a key role in cellular immune responses. The population diversity of MHC molecules is extremely large: for some MHC loci, over one hundred different alleles have been identified. The mechanisms behind the selection for MHC polymorphism have been debated for over three decades. A commonly held view is that MHC polymorphism is due to selection favoring heterozygosity. It has been argued that selection for heterozygosity alone cannot explain the large MHC diversity observed in nature, and that ``frequency-dependent selection'' is required. We simulation evolution by developing a genetic algorithm in which hosts and pathogens co-evolve. The analysis demonstrates that selection involving rapid evolution of pathogens can account for a much larger MHC diversity than selection for heterozygosity alone can.
    ICBW04 12th December 2001
    11:30 to 12:30
    Genetic, dynamic and functional definition of the efficency of the anti-viral T cell response
    In infection with the human T cell leukaemia virus (HTLV-I), there is a powerful T cell immune response to one of the viral proteins, called Tax. We have obtained evidence that the strength of this immune response determines the "set point" of HTLV-I load in the blood, which can vary between HTLV-I-infected people by more than 1000 times, but is constant in each infected person over time. Our evidence is derived from experimental data on genetic variation in the host and in HTLV-I, cellular immunology, and DNA expression microarrays. We have used dynamical approaches a) to reconcile the evidence of persistent HTLV-I replication with the observed conservation of HTLV-I sequence; b) to suggest a reason for the apparent threshold in HTLV-I load above which many people develop chronic inflammatory diseases; c) to explain the observed variation between individuals in the frequency of anti-HTLV-I T cells, and d) to test the consequences of HTLV-I-induced T cell death on the control of HTLV-I replication. The aims of this work are to define the concept of antiviral "T cell efficiency" in genetic, dynamical and functional terms, and to test experimentally whether this "efficiency" determines the outcome of HTLV-I infection.
    ICBW04 12th December 2001
    14:30 to 15:30
    Word frequency distribution under the restriction avoidance
    Restriction enzymes of bacteria cut the unmodified recognition sites of DNA, thereby protect bacteria from the infection by phage. This imposes a strong selective pressure on the phage genome sequences. For example, the Bacillus phage phi1 genome has much fewer restriction sequences of Bacillus restriction enzymes than their random expectations. To answer the evolution of phage genome under the selection by bacteria restriction enzymes, a simple model for the evolution of binary or nucleotide sequences is proposed. The model shows that not only the frequency of the restricted sequence itself in the genome, but also that of the other subsequences (words) will be largely deviated from the random expectations. The pattern of word frequency distribution sensitively depends on the type of restricted sequence. If the restricted sequence is of the singlet repeat type (e.g. 000), the frequency of a 3-letter word is largely explained by its Hamming distance from the restricted sequence -- the farther is the Hamming distance of the word from the restriction sequence, the more is its abundance. However, quite unexpected word frequency distribution arises if the restricted sequence is of the other type (e.g. 001 or 010). The abundance of words is largely influenced by the vulnerability to restriction of partially overlapped adjacent words. For example, when 001 is the restriction sequence, both 000 and 100 become quite rare, whose frequencies approach to 0 as the genome size increases; whereas 101, which is only one-step distant from the restricted word, becomes quite common. A new theoretical framework is proposed to explain such peculiar distribution of words under restriction avoidance, which enable us to count the exact word frequency of any word in the 'feasible' sequences. A sequence is called feasible here if it contains no restriction site in any position (i.e. the feasible sequences are that survive under a strong selection). The fraction of feasible sequences in all random sequences exponentially decays towards zero as the genome size increases (e.g. if the restriction sequence is 001, the number of feasible sequences in all binary sequences of length n equals the (n+3)rd term of Fibonatti series minus 1, which gives the fraction of feasible sequences decaying with n as (0.81)^n). In the light of these results, I discuss the optimal recognition sequence of restriction enzyme to fight against phage, and the mutation and substitution loads and the fitness landscape of phage subject to such selection pressure imposed by a restriction enzyme.
    ICBW04 12th December 2001
    16:00 to 17:00
    Inequalitites during life and death of T cells
    T cell selection during an immune response is being increasing observed with modern techniques, eg the (specific) T cell receptor (TCR) chain useage and its diversity alters throughout an immune response, and TCR avidity for the agonist ligands undergoes distinct focusing from a primary to secondary response. We explore physiologically structured models of T cell growth and T cell death to explain these observations. We demonstrate that significant selection of T cells can occur through heterogeneous expression of cytokine receptors and competition for growth/survival cytokines.
    ICBW04 13th December 2001
    09:00 to 10:00
    Epidemics at different spatial scales, from social behaviour to community dynamics
    ICBW04 13th December 2001
    10:00 to 11:00
    The roles of chance and spatial structure within host evolution of HIV
    The way in which HIV evolves varies greatly between different infected hosts. I will discuss the role of deterministic factors, such as the viral genotype and the strength of immune responses, and stochastic factors in generating this variation. In particular, I will consider the processes of genetic drift, stochastic fluctuations in gene frequencies due to finite population size, and genetic draft, stochastic fluctuations in gene frequencies due to linkage to positively selected mutations. The bulk of viral replication occurs in highly spatially structured lymphoid tissues. I will discuss the impact of spatial structure on genetic drift and draft.
    ICBW04 13th December 2001
    11:30 to 12:30
    Waves and sparks in the spatio-temporal dynamics of microparasitic infections
    ICB 13th December 2001
    14:00 to 15:00
    Meeting with ICB Organisers and the Wellcome Trust
    ICBW04 13th December 2001
    15:00 to 15:30
    Presentation on funding opportunities
    ICBW04 13th December 2001
    16:00 to 17:00
    Optimising the effectiveness of T cell activation
    We will discuss the role of negative selection, MHC and presentation selectivity in optimising the effectiveness of T cell activation. We will show how this leads to MHC restriction and specific presentation strategies as well as upper and lower bounds on the number of MHC isoforms. We will also discuss the relation between negative selection and the need for peripheral tolerance mechanisms by analysing the effectiveness of negative selection as a function of the statistical structure of antigen presentation in terms of ubiquity and presentation propensity.
    ICBW04 14th December 2001
    09:00 to 10:00
    S Ruan Multiple parameter bifurcations in ecological and epidemiological models
    I will show that many biological systems such as predator-prey models with harvesting, SIRS epidemiological models with nonlinear incidence rate, epidemiological models with constant removal rate of the infectives, predator-prey models with nonmonotonic functional response, predator-prey models with nonlinear mortality rate, etc. exhibit codimension two bifurcations which include Hopf, saddle-node, and homoclinic bifurcations. Examples of codimension three bifurcations will also be given.
    ICBW04 14th December 2001
    10:00 to 11:00
    M Pascual Modified mean-field models and self-organisation in spatial systems for antagonistic interactions
    A simple modification of the mean-field equations provides an accurate approximation of the macroscopic dynamics of predator and prey densities in an individual-based model that is both stochastic and nonlinear. This approach modifies the parameters but preserves the functional forms of the mean-field equations in spite of the elaborate spatial patterns present in the system. The spatial patterns reduce the per-capita rates of predation and prey growth but do so in a way that is both simple and specific. In particular, these rates become those one would expect in a well-mixed system but with a smaller `effective neighborhood' of interaction. A connection is described between the proposed modified mean-field equations and the geometry of the system. The cluster geometry is characterized by power-law scalings that appear robust to changes in the parameters and in the microscopic rules specifying growth and inhibition. Implications for models of macroscopic dynamics when microscopic behaviour is not well known are discussed.
    ICBW04 14th December 2001
    11:30 to 12:30
    Discussion and Closing remarks
    University of Cambridge Research Councils UK
        Clay Mathematics Institute London Mathematical Society NM Rothschild and Sons