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<Graduate Open Day>
- CoMPLEX will be at the Graduate Open Day of the Faculty of Mathematics and Physical Sciences on 24 January 2014
A new publication by PhD student Nicolas Jaccard
This page lists the poster presentations that will take place during the conference. For posters whose author agreed to online publication, clicking the title will lead you to the abstract of the poster.
|Ashworth||William||Spatial Heterogeneity in Models of Glucose Metabolism|
|Atkinson||Sophie||The Fission Yeast Non-Coding Transcriptome|
|Banerji||Chris||Network Rewiring in Disease and Differentiation|
|Bartlett||Tom||Epigenetics, stem cells and cancer biology|
|Best||Katharine||Inferring parameters of the T cell receptor repertoire|
|Botcharova||Maria||Detecting the presence of long-range temporal correlations in a time-varying measure of phase synchrony|
|Davison||Claire||Metabolism and neuronal excitability: Replication of a model and its potential interest to the study of brain activity in preterm infants.|
|Dee||Ryan||Seeding human umbilical vein endothelial cells on a sterilised biodegradable nanocomposite polymer|
|Heussen||Raphaela||Mathematical modeling of the Zebrafish circadian clock|
|Hoare||Rollo||A novel mechanistic model for CD4 lymphocyte reconstitution following paediatric haematopoietic stem cell transplantation|
|Khalilgharibi||Nargess||The Short Timescale Mechanics of Cell Monolayers: An Experimental-Computational Approach|
|Lehtinen||Sonja||Stress induces remodelling of yeast interaction and co-expression networks|
|Lucas||Tim||The phylogeography of henipah virus|
|Manson||Daniel||Cognitive spatial grids change size during familiarization with a new arena|
|Moorcroft||Elizabeth||Paws for thought|
|Protonotarios||Emmanouil||Psychophysics of the perception of apparent order in 2D point patterns|
|Stanley||Robert||ARF the story: A validated model of PI4P5K activation|
|Strandkvist||Charlotte||The nature and function of junction length fluctuations within a developing epithelium|
|Symonds||Janine||Mathematical Modelling of Purine Metabolism in HL-60 Cells|
|Walsh||Claire||Compressed collagen hydrogels- An in vitro model for decompression sickness|
|Walsh||Gordon||The construction and parametrisation of a mathematical model of phosphoinositide metabolism|
Spatial Heterogeneity in Models of Glucose Metabolism
Numerous models of glucose storage in the liver have been developed in recent years with the most detailed models including almost all the hormones, proteins and enzymes involved in storing glucose as glycogen and lipids. However, existing models focus on just one hepatocyte (liver cell) and the surrounding blood and presume that, by multiplying up, this represents the liver as a whole. It is known that there are gradients in hormones, nutrients and oxygen supply across the liver and that these lead to specialization of the cells with the more oxygen and nutrient reliant processes performed closer to the artery supplying the organ. We are building a compartmental model of the liver lobule (functional subunit of the liver) to investigate the importance of this heterogeneity in regulating blood glucose.
Network Rewiring in Disease and Differentiation
“Genes do not act in isolation""; this is a simply stated fact but the ramifications are profound.
Unravelling the rich tapestry of genome wide genetic interaction is akin to unmasking some of the fundamental mysteries of biology; for within it is written the hidden genetic conspiracies which give rise to each and every possible phenotype.
Interrogation of these collaborative gene dynamics is essential to reveal the molecular mechanisms of poorly understood diseases, where the genotype to phenotype link comprises of an incestuous web of complex genetic relations, far too convoluted to be linearly deducible.
Systems biology and network concepts, particularly the conceptual framework of differential networks and network rewiring, allow higher order, unbiased analysis of gene expression data, to elucidate such pathological mechanisms in complex diseases
We have developed and validated a novel differential network methodology, for the analysis of gene expression data of diseased and control samples capable of extracting a subset of the human interactome, displaying a complete map of perturbed signalling in the disease.
We applied this methodology to a meta analysis of gene expression data for the most prevalent muscular dystrophy FSHD, and have uncovered and preliminarily experimentally validated novel therapeutic targets. We also adapted this methodology to the analysis of cell differentiation time courses, and validated it in a study of HL60 progenitor cells into neutrophils.
In a more general theoretic context, we have adapted the classical information theoretic measure transfer entropy for the interrogation of paths of high information transfer in a weighted network, constructing a novel general measure we call network transfer entropy, which we have validated in the context of phosphorylation networks. We have also demonstrated that in the process of constructing this measure, we create a space of dynamics of weighted networks, which admits a metric structure. We prove that convergence of the weighted structure of a network in a class of matrix metric spaces implies convergence of the corresponding dynamics in our new metric space. This result establishes that notions of drug treatment to modify, say protein binding affinities, with the aim of reaching a target gene expression regime are coherent within our framework.
Detecting the presence of long-range temporal correlations in a time-varying measure of phase synchrony
Neural synchronisation plays a critical role in information processing, storage and transmission. Therefore, characterising the temporal dynamics of synchronisation is of great interest.
It has been suggested that critical systems exhibit power law statistics of phase synchronisation. However in a recent paper, we demonstrated that such statistics are not a reliable marker of criticality as pooling in a non-critical system can also produce them.
Here, we present an alternative method to characterise complexity in temporal patterns of synchronisation between signals. We apply detrended fluctuation analysis (DFA) to assess presence of Long-Range Temporal Correlations (LRTCs), a property that has been linked to criticality, in time-series of pairwise phase differences. We suggest that our method can also be applied to biological data.
We analysed a version of the Kuramoto model, with spatially embedded oscillators, and two Fourier components in their phase interaction function. The model generates brain-like oscillations. We focus on a regime of winnerless competition and show the presence of LRTCs for parameter values which correspond to non-trivial synchronisation patterns.
Seeding human umbilical vein endothelial cells on a sterilised biodegradable nanocomposite polymer
Congenital Heart Disease (CHD) is the most prevalent of congenital defects in neonates. Current treatment methods for the most severe cases require surgical implantation of non-degradable grafts, which lack growth potential to grow with the patient, leading to complications. This indicates the need for a tissue engineered approach. We investigate the use of a synthetic biodegradable nanocomposite polymer to be used as a scaffold in such an approach. Isolated human umbilical vein endothelial cells (HUVEC) are cultured on tissue culture plastic before seeding on to the polymer. The HUVEC appear to attach to the surface of the polymer. The effects of sterilising the polymer by autoclaving and ethanol are investigated for their effects on mechanical properties and surface chemistry.
A novel mechanistic model for CD4 lymphocyte reconstitution following paediatric haematopoietic stem cell transplantation
Before a haematopoietic stem cell transplant (HSCT), a child will usually be given a conditioning regimen to reduce or ablate the host immune system in order to prevent graft rejection. Following HSCT, long-term outcomes and short-term complications are associated with the rate and extent of recovery in the child’s immune system. Studying immune reconstitution in children is challenging as the rapidly developing immune system results in large variations in expected CD4 T-cell counts for age. This work presents a new mechanistic model describing the reconstitution of total-body CD4 T-cell count with time in children following an HSCT.
The fundamental model has three parameters representing the initial CD4 count, thymic output of CD4 cells, and the net loss rate of CD4 cells. The model is made more mechanistic in three ways: (1) accounting for age-related changes in the thymus with a functional form for thymic output; (2) allowing for thymic output not recovering production immediately after HSCT; (3) including the effects of competition for homeostatic signals leading to changes in the net loss rate with cell quantities. We apply this model using nonlinear mixed effects modelling to longitudinal data collected by the bone marrow transplant unit in Great Ormond Street Hospital.
The Short Timescale Mechanics of Cell Monolayers: An Experimental-Computational Approach
Despite being the simplest tissues, one-cell-thick monolayers play critical parts in the development and physiology of multicellular organisms. Their function requires them to generate internal forces during embryonic morphogenesis, and in adult tissues, to act as a physical barrier, separating the interior of the organism from its exterior and resisting external forces. How do monolayers fulfil these roles? To answer this question, a better understanding of the mechanical properties of monolayers is needed.
By combining experimental and computational techniques, I aim to investigate these properties in short timescales. Using a recently developed testing device , I will study the response of monolayers to different amounts of stress and strain. I would also like to understand how much of this mechanical response is passive. To answer this, I will block metabolic pathways of the cells in the monolayer and compare their behaviour to normal living monolayers under stress. Parallel to the experiments, I will develop a finite element model of the tissue, which will make it possible to understand the experimental results in a physical theoretical framework.
Harris AR, Peter L, Bellis J, Baum B, Kabla AJ, Charras GT.Characterizing the mechanics of cultured cell monolayers. Proc Natl Acad Sci USA.2012;109(41):16449–54.
Stress induces remodelling of yeast interaction and co-expression networks
External insults (“stress”) cause rapid and widespread rearrangement of cellular regulatory systems, allowing organisms to survive environmental changes. We show that exposure to stress remodels protein interaction and gene expression networks, inducing a shift towards a more modularised structure. This could represent an increase in network robustness and/or the emergence of more specialised functional modules.
The phylogeography of henipah virus
Henipah is a genus of emerging zoonotic diseases which can cause high rates of mortality in humans. I use georeferenced genetic data to examine the transmission of the virus within its fruit bat reservoir. I find that transmission rates are high within regions but low between continents.
Paws for thought
Felidea, the cat family, is made up of 37 species of which half are threatened. Many of these species have intricate pelage patterns making individual recognition possible. This, with the advent of camera-trapping, technology allows for a recapture rate of individuals to be calculated, and thus for population size and density to be monitored. The number of studies using these methods has increased dramatically over the last 15 years.
Here I review the results of 52 camera trapping studies and evaluate capture-recapture mathematical models used to estimate wild cat density. I explore current camera survey designs and assess whether some of the assumptions underlying analyses may be invalidated under realistic patterns of ranging behaviour. Now that camera trapping is commonplace, identifying which assumptions are at risk of being broken, and understanding the consequences of such violations, are vital to conservation work on wild felids.
Monitoring ecosystems at the species and individual level can provide meaningful insights into ecosystem health, informing and directing conservation efforts. To allow such analysis, animals need to be detected, captured and identified. Traditionally this has involved physical capturing (which can be time-consuming, inefficient and expensive), but automating the process where possible is highly desirable. Using camera and audio traps is a step towards this automation.
Some animals are more amenable to acoustic monitoring; small, fast, marine or nocturnal animals that vocalise or call may be much easier to record and recognise by sound than by sight. Bio-acoustic identification of terrestrial animals has mainly concerned birds and, to a lesser extent, crickets; the bulk of this literature is heavily founded on the older and more established field of automatic human speech recognition. The acoustics of many mammals can be treated similarly to humans due to the similar underlying mechanisms. This is not the case for echolocating animals, such as some bats or dolphins; these species have evolved to use sound differently.
In particular, bats are an interesting case-study; bat species make up 20% of all mammals and their habitats are globally distributed, providing important indicators on habitat health. Acoustic identification of bats has been used as a monitoring tool for decades, though we are yet to reach anything close to a continental-scale, all-inclusive reliable species classifier, and progress is far behind other taxa. This could be partly attributed to the lack of mechanistic approaches being developed for echolocation call characterisation, with the traditional method of measuring spectrograms still being common practice. My current focus is investigating mechanistic feature selection for automated acoustic species identification of bats.
ARF the story: A validated model of PI4P5K activation
The activation by ARF of enzymes PLD andPI4P5K and the `cross-talk' regulation by their products is a novel motif in lipid signalling. I have constructed a simplified mass-action model for PI4P5K with substrate affinity and activation by ARF, and parameterised this model experimentally using a kinase assay.
Compressed collagen hydrogels- An in vitro model for decompression sickness
Decompression sickness (DCS) is a potentially fatal condition caused by the formation of inert gas bubbles in tissues which has been subjected to a rapid reduction in ambient pressure. DCS results from the response of organ systems to these bubbles. Initially, relatively mild symptoms occur in the skin, lymphatic or musculoskeletal systems; these may be followed, by more severe effects in the central nervous system.
Susceptibility to bubble formation and growth in different tissues varies, but little is known about how this relates to the clinical progression of DCS. Difficulties in collecting relevant experimental data are a major obstacle to furthering our understanding of DCS. By engineering Collagen type I hydrogels, with varying density and biomimetic matrix composition, we have developed an in vitro system for studying the condition. We have varied specific parameters we hypothesize to be of significance to bubble dynamics, namely, tissue elasticity and anisotropy, cell type and perfusion level. A pressure vessel we have designed, allows for the microscopic observation of bubble dynamics in these constructs during a simulated dive. This system enables a systematic and quantitative investigation of the tissue parameters that affect bubble growth.
In parallel with this a mathematical model of bubble dynamics in soft tissue has been developed. Using data derived from cavitation rheology experiments, the model can be used to simulate the same dive profiles as the pressure chamber, providing a direct comparison to the experimental results.
Initial bubble growth shows a dependence on tissue elasticity, as controlled by matrix density; and anisotropy, as controlled by cyclic loading.
Chappell, Michael. Modelling and Measurement of Bubbles in Decompression Sickness. Diss. University of Oxford, 2006.
Brown, Robert A., et al. ""Ultrarapid Engineering of Biomimetic Materials and Tissues: Fabrication of Nano‐and Microstructures by Plastic Compression."" Advanced Functional Materials 15.11 (2005): 1762-1770.
Zimberlin, Jessica A., et al. ""Cavitation rheology for soft materials."" Soft Matter 3.6 (2007): 763-767.
The construction and parametrisation of a mathematical model of phosphoinositide metabolism
The Phosphatidylinositol (PI) cycle is a ubiquitous metabolic and signalling pathway in eukaryotes, it plays a major role in mediating hormone and growth factor signalling. Without extracellular signal, this metabolic cycle rests at steady state concentration levels with a basal flux. Extracellular signals cause a dynamical shift in the cycle that increases total flux and cause different temporal behaviours. In principle several internal positive feedback loops within the cycle allow for a range of complicated behaviours.
A general kinetic model of the PI cycle has been constructed using a system of mass action ODEs and algebraic relations (such as Hill functions). Individual rates and concentration parameters have been obtained from a combination of existing literature, experimental data and computational estimation, the model reproduces the qualitative and quantitative results seen in experiments. The model has been used to predict metabolic behaviour under drug stimulations (such as Lithium) and 13-C NMR and TLC have been used for parameterisation and to produce data to validate the computational predictions.
Page last modified on 03 may 13 17:02