2012 intake

 
Sami Bouremoum Pattern regularity and scale in biology
Rory Bufacchi Investigating the specificity of the cortical responses elicited by stimuli of different modalities in humans
Ruth Eccleston Dynamics of epitope presentation on MHC Class I molecules following viral infection
Elizabeth Gallagher Evolutionary game theory models for the origins of agriculture and the rise of social inequality
Janos Hodsagi Plasticity of biological networks
Nicola Lockwood Global imaging of physiological and pathophysiological angiogenesis in live zebrafish using optical projection tomography
Adedeji Majekodunmi CD4 T cell immune reconstitution in HIV infected children in response to antiretroviral therapy 
Federico Mancinelli Investigating cognitive control in mental illnesses
Jeremy Owen Evolution of reciprocal sex from lateral gene transfer in early eukaryotic evolution
Jaspal Puri Magneto-Mechanical Actuation of Muscle 
Arunas Radzvilavicius Mitochondrial inheritance in the evolution of complex multicellular organisms with germline-soma differentiation

Mark Ransley

Developing Wearable Assistive Materials (WAM) for Orthopaedic Applications
Lourdes Sri Raja Elucidating the structure of the combined regulatory and signaling network controlling haematopoietic stem cell differentiation
Matthew Topping Mechanosensory pathways as potential targets for the control of insect-borne diseases
Lucy van Dorp Investigating Processes Driving Genetic Diversity Among Human Populations

Sami Bouremoum ^

Pattern regularity and scale in biology

The near-synonyms – regularity, order, symmetry and pattern – are important aspects of image structure. Tools for their analysis are relatively undeveloped, the focus having generally been on limited conceptions of symmetry (e.g. global reflectional only) and patterns which are near perfect symmetry. We will working on definitions of local quasi-symmetry in natural images and how to quantify them. We will also investigate the problem of scale in image symmetries and hope to obtain a unique scale or a systematic way of obtaining it for any natural image. We will also produce computer software that autonomously computes local symmetry in natural images.

By imaging developing embryos as they reach the end of development it is possible to see order emerging within tissues. This pattern refinement occurs at different temporal and spatial scales for different processes in the same tissue. To shed light on this process of refinement, the aim of this project is to develop algorithms that can automatically identify ordering events at different temporal and spatial scales in the developing fly.

Sami Bouremoum

Rory Bufacchi ^

Investigating the specificity of the cortical responses elicited by stimuli of different modalities in humans

Whether primary sensory cortices are essentially multisensory or whether they respond to only one sense is an emerging debate in neuroscience.

The group I am working with recently used multivariate pattern analysis (MVPA, or machine learning) of functional magnetic resonance imaging data in humans to demonstrate that simple and isolated stimuli of one sense elicit distinguishable spatial patterns of neuronal responses, not only in their corresponding primary sensory cortex, but in other primary sensory cortices (Liang et al Nature Comms 2013). These results indicate that primary sensory cortices, traditionally regarded as unisensory, contain unique signatures of other senses, which prompts a reconsideration of how sensory information is coded in the human brain.

The planned research aims at further characterising the specificity of the response from different cortical areas to stimuli of different sensory modalities, and also exploring the amount of stimulus features that are encoded in the response elicited by stimuli of one given sensory modality in non-pertinent primary sensory cortices. The research will involve the collection of electrophysiological (EEG/MEG) and metabolic (fMRI) functional neuroimaging data, and their analysis using techniques like machine learning.

Rory Bufacchi

Ruth Eccleston ^

Dynamics of epitope presentation on MHC Class I molecules following viral infection

Major Histocompatibility Complex (MHC) molecules make up part of the cell-mediated adaptive immune system in which antigen-specific defence mechanisms are acquired against threats such as viruses and tumours. MHC-I alleles present short sequences of proteins, known as peptides, which are cleaved in the cytoplasm primarily by the proteasome. Some cell surface peptide-MHC complexes are able to activate cytotoxic T lymphocytes (CTLs) through interactions with T cell receptors (TCR). The probability of CTL activation is determined by the peptide cell surface abundance and the binding affinity between the presented peptide and the TCR. Those peptides which activate T lymphocytes are known as epitopes. In this project we will be focussing on the role of the timing of the presentation of viral epitopes on the cell surface in determining the immune response. This project aims to combine a kinetic model of the pathway of viral peptide presentation from supply to the Endoplasmic Reticulum (ER) to the peptide-MHC complex cell surface abundance, with the production of defective ribosomal proteins (DRiPs) which are implicated in many viral infections. The kinetics of DRiP production will be guided by experimental data and the epitope dynamics of multiple viruses will be compared. It is hoped that such a model will aid the understanding of epitope production and presentation and the role of timing in determining the immunodominance of certain few viral epitopes despite the large variability in peptides ligands at the surface. Understanding what leads some epitopes to become immunodominant may inform the design of peptide vaccines against viruses and other novel therapies.

Elizabeth Gallagher ^

Evolutionary game theory models for the origins of agriculture and the rise of social inequality

The origin of agriculture in southwest Asia at the end of the last Ice Age and its subsequent spread as the main form of human subsistence was one of the most important transformations in human evolution and continues to have major consequences today for many aspects of human health and ways of life (e.g. Bocquet-Appel 2011, Laland et al. 2010). Recent work has challenged behavioural ecology explanations that have seen it as the endpoint of a long-term expansion of human diet breadth to incorporate lower-ranked resources with increased processing costs (Bowles 2011). Instead Bowles and Choi (n.d.) have developed an evolutionary game theory model of the returns from hunting and gathering versus farming in the context of different systems of property rights by comparing the payoffs of three different strategies – Sharer, Civic and Bourgeois – in relation to the different subsistence systems and the returns expected from them in different climatic conditions. However, there are weaknesses in the Bowles-Choi model. The aim of this project is to develop alternative evolutionary game theory models for the origins of agriculture and go on to model the payoffs to different property inheritance systems and their effects on inequality (cf. Borgerhoff Mulder et al 2009).

Elizabeth Gallagher

Janos Hodsagi ^

Plasticity of biological networks

Plasticity and rigidity of networks is a well-known bimodality in biology. Whether plastic or rigid behaviour is favourable depends on the environmental conditions. As a result, organisms need to hit a balance between the two modes of behaviour. This project aims for a better understanding of plasticity of networks. The projects involves applying the concept of dynamic network entropy to investigate changes in plasticity in various biological networks. Dynamic network entropy was shown to increase in cancer, which is in a special focus of this project. However, it is unclear how plasticity change during the course of cancer development. According to a recently proposed hypothesis, cancer development is similar to cellular learning in that a first, exploratory phase of increased plasticity is followed by a more rigid phase at later stages of the process. It is our intention to test for the validity of the two-stage cancer hypothesis, and expand and explore this area in a general sense. On the other side, we are interested in proposing self-contained models of the plasticity of networks.

Janos Hodsagi

Nicola Lockwood ^

Global imaging of physiological and pathophysiological angiogenesis in live zebrafish using optical projection tomography

Cancer research is in its prime, whereby in vivo studies are incredibly important due to global processes often being involved in key cancer hallmarks, which is particularly true for angiogenic diseases. The majority of previous in vivo studies of cancer have required the model organism to be sacrificed to determine the tumour pathology and molecular alterations. Therefore, genetic variation between the organisms at each time point was problematic, and so multiple sacrifices were required. The interdisciplinary approach of Optical Projection Tomography can avoid this through observing the progression of individual tumours within live zebrafish over time, therefore providing immense accuracy.

Vascular development and inflammation are critical for progression of the disease state and so act as important targets for drug discovery. Developing this system towards a new stage that can characterise these events at a molecular and signalling level is likely to dramatically improve the way in which global cancer development and cancer cell signalling can accurately be determined. I aim to do this through developing appropriate 3-D imaging techniques including optical projection tomography and establishing methodologies, including generation of novel transgenic zebrafish lines, for the study of angiogenesis.

Nicola Lockwood

Adedeji Majekodunmi ^

CD4 T cell immune reconstitution in HIV infected children in response to antiretroviral therapy

The number of T and B-lymphocytes in an individual increases in a predictable manner during childhood and then stays remarkably constant throughout adult life in spite of declining production, peripheral cell division and unpredictable responses to infection. The complex homeostatic mechanisms involved are beginning to be understood through combined experimental data, clinical trials and mathematical/statistical modelling approaches. In HIV infection, CD4+ T cells are lost causing profound immunodeficiency, susceptibility to infection and death. In response to treatment with antiretroviral drugs, normal homeostatic mechanisms in the body strive to replace the lost CD4 T cells by production of new T cells in the thymus and ‘homeostatic’ T cell proliferation in the periphery (lymphoid tissues) but often do not reconstitute to normal levels.

The aim of this project is to develop mathematical models capable of predicting the levels of CD4 counts in children infected with HIV. Non-linear mixed effect models will be used to compensate for individual variability of CD4 counts seen amongst patients infected with HIV.

The following questions will be answered:

 1. How good are the models generated at predicting CD4 counts when children become adults?

 2. What is the impact of treatment interruption on long-term CD4 cell reconstitution?

Adedeji Majekodunmi

Federico Mancinelli ^
Investigating cognitive control in mental illnesses

The nascent field of computational psychiatry stems from an effort to understand mental illnesses in a new way, through large scale mathematical and computational modelling. Modellisation can bear different levels of abstraction, from the algorithmic level borrowed by the Machine Learning framework, to the neural models belonging to computational neuroscience and Reinforcement Learning. Here, we harness the Reinforcement Learning framework in order to explore cognitive control in mental illnesses. We focus on the way that an illness can alter the way we make decisions, which can be both endogenous (i.e. decisions on the way we use our working memory) or exogenous, decisions on actions. If the mechanisms and metrics which govern these choices are corrupted, the decisions taken will not be normative. This is important in a range of conditions which affect impaired inhibition and impulsivity and also the deployment of attention. Schizophrenia will most likely be our target.

Federico Mancinelli

Jeremy Owen ^

Evolution of reciprocal sex from lateral gene transfer in early eukaryotic evolution

Supervisors:
Andrew Pomiankowski
Nick Lane (GEE)

Evolutionary adaptation to new or changing environments cannot happen without genetic variation, which is the source of new, fitter phenotypes in populations of reproducing organisms. The division of higher organisms into two sexes is a strategy to ensure genetic diversity; mixing the genes of two individuals during sexual reproduction produces offspring with more varied genotypes, increasing the chances of novel adaptive phenotypes. Prokaryotes reproduce asexually, but maintain genetic diversity by processes known collectively as lateral gene transfer, involving the direct movement of genetic material between unrelated organisms rather than the recombination of the parents’ genetic information in the offspring.

Eukaryotes, including all sexually recombining organisms, evolved from symbiotic partnerships between prokaryotes, so recombination presumably first originated in organisms that initially used lateral gene transfer to ensure genetic variation. Using mathematical and computational models, I will investigate how events in the early evolution of eukaryotes might have favoured recombination over lateral gene transfer, and why modern-day prokaryotes and eukaryotes use such different mechanisms to ensure genetic variation.

Jez Owen

Jaspal Puri ^

Magneto-Mechanical Actuation of Muscle

Force produced by permanent magnets in close proximity to the body offers an array of potential biomedical applications. One aspect involves the combined use of permanent magnets to control the orientation, migration and growth of cells grown with magnetic materials via a process termed magneto-mechanical actuation.

My PhD project builds on preliminary data that has shown it is possible to measure magneto-mechanical actuation using a combination of cell culture, in vitro and in silico modelling, and image analysis techniques. It is anticipated we will elucidate the parameters needed to successfully achieve magneto-mechanical actuation for a variety of muscle groups found throughout the body whilst also investigating the mechanical properties of explanted muscles by means of uniaxial mechanical testing. The data we generate will be used for in in vitro and in silico modelling of force distributions across cell populations cultured with magnet materials and exposed to different combinations of permanent magnets.

Such work may well significantly impact the field of tissue engineering as well as potentially forming the foundations of novel muscular regeneration therapies.

Jaspal Puri

Arunas Radzvilavicius ^

Mitochondrial inheritance in the evolution of complex multicellular organisms with germline-soma differentiation

Supervisors:
Andrew Pomiankowski
Nick Lane (GEE)

The emergence of multicellularity in eukaryotes transformed the mapping between mitochondrial fitness in germ line and adult viability by introducing the effects of mutation accumulation, segregation of organelles, division of labour and differentiation. These changes have strong effects on the favoured pattern of mitochondrial inheritance and introduce several costs and benefits of having an isolated germ line. We propose, that

mitochondrial fitness and mutation might be central processes in the development of complex multicellular features, including early germ line definition. The hypothesis can be tested by investigating mitochondrial evolution trends in basal metazoans, higher animals and plants. Results of our computational modelling will possibly lead to the theory accounting for the role of extra-nuclear genomes in evolutionary transitions following the emergence of complex cell and multicellularity, explaining the existence of two sexes, germ line/soma distinction and patterns of cellular ageing.

Arunas Radzvilavicius

Mark Ransley ^

Developing Wearable Assistive Materials (WAM) for Orthopaedic Applications

Supervisors:
Prof. Mark Miodownik (Mechanical Engineering, Institute of Making)
Mr. Peter Smitham (Institute of Orthopaedics and Musculoskeletal Sciences)
UCL Wearable Assistive Materials group

My research concerns the development of a novel robotic exoskeleton technology, with the ultimate aim of providing an alternative to wheelchairs, walking sticks and other mobility aids. Using chemical actuators and magnetic gels currently in development by the WAM team, we intend to create a material that is thin and light enough to be worn comfortably, whilst its flexibility and shape can be rapidly adjusted with small ionic potentials.

I am investigating the various ways in which the aforementioned drivers could be incorporated into a wearable material, the nature of the control this would deliver, and its applicability to human physiology. Once a suitable control system has been designed, I will be prototyping a proof-of-concept device at the Institute of Making. Working closely with patients at the Institute of Orthopaedics and Musculoskeletal Science, the intention is to be able to produce patient specific Wearable Assistive Materials using an advanced bespoke 3D printer.

Mark Ransley

Lourdes Sri Raja ^

Elucidating the structure of the combined regulatory and signalling network controlling haematopoietic stem cell differentiation

Supervisors:
Dr. Geraint Thomas
Dr. Chris Barnes
Dr. Simone Severini

Haematopoietic stem cells are perhaps the most studied of all stem cell types. Despite this, the underlying gene regulatory networks that control proliferation and differentiation, and the signalling systems that process the intracellular and environmental cues, remain to be elucidated. Understanding how to manipulate these processes has wide implications for therapeutics and also serves as a model for the control of other multi-potent stem cell types.

This project has two distinct parts.  The first phase will involve the building, and refinement of, a mathematical (computational) model of aspects of the regulation of blood stem cell differentiation.  The second phase requires experimentation to validate the new models.

Lourdes Sri Raja

Matthew Topping ^

Mechanosensory pathways as potential targets for the control of insect-borne diseases

Insect-borne infectious diseases are one of the major plagues of humanity, annually causing millions of deaths. It always starts the same way: a female mosquito bites a human, infecting them with a disease-causing pathogen. Controlling mosquito populations and preventing them from biting humans is therefore a primary goal in global disease management.

Disease transmission is inextricably linked to the biology of mosquitoes. My PhD project will study the mechanosensory bases of mosquito blood-feeding behaviour. It seems very likely that, in order to insert their proboscis into the human skin, mosquitoes rely on sensory feedback from mechanosensory organs, like e.g. chordotonal organs (ChOs). We will test this by ablating chordotonal organ function using chordotonal-specific insecticides.

Mechanosensory, and specifically chordotonal, signalling, however, is also a crucial component of the animals’ air-borne courtship, and copulatory, behaviour. The same strategy that impairs the animals’ ability to insert their probosces into human skin could thus also directly impact the animals’ reproduction rate.

Results and implications of these experiments will be analysed with newly devised computational models of disease transmission, using the degree of mechanosensory impairment as a novel model parameter.

We anticipate that our approach will lead the way to new strategies of vector control.

Matthew Topping

Lucy van Dorp ^

Investigating Processes Driving Genetic Diversity Among Human Populations

Although it is well established that DNA varies substantially among different world-wide human groups, the principal forces driving this genetic diversity are not well understood. This project aims to describe genetic patterns among a wide range of human groups and characterize the primary historical, anthropological and sociological factors that contribute to observed levels of genetic diversity among these groups. A novel statistical methodology will be developed and applied to available data stored at UCL, which includes genome-wide DNA interrogated at hundreds of thousands of single-nucleotide-polymorphisms (SNPs) in hundreds of world-wide human subjects. These data resources also include detailed sociological and genetic information from the world's largest DNA collection of individuals from Ethiopia, an important country for studying the origins of anatomically modern humans and their subsequent dispersal from Africa throughout the rest of the world. Through merging these unique methods and diverse datasets, this project aims to answer a number of important questions about human evolution.

http://www.ucl.ac.uk/~ucbpvan/index.html

Lucy van Dorp

Page last modified on 08 oct 13 09:42