8. Modelling host-virus metabolic interaction
Funding for this PhD studentship comes from DSTL, under their research program on pathogens posing a biothreat. Parasites have evolved elaborate mechanisms for manipulating the host environment to improve their own survival and growth. In particular, viruses have evolved strategies to down-regulate expression or inhibit proper folding of specific host proteins. These strategies modulate host cell physiology and metabolism. These findings raise the possibility that host metabolism could be modulated in such a way so to resist pathogen-mediated reprogramming, and thereby allow for increased host resistance. This project builds on our expertise in analysing viral infection of host cells through a modelling approach that treats the virus-infected cell as a single metabolic system. Timeframe: 2014-2017.
7. Engineering synthetic microbial communities for biomethane production
This project is funded by BBSRC as part of their 20m investment in synthetic biology. One of the six strategic LoLa's (longer and larger grants), this 5 year project brings together an interdisciplinary team of engineers, microbiologists, evolutionary biologists, synthetic biologists, and bioinformaticians to understand natural microbial communities and engineer synthetic ones. The communities we will focus are those that underline anaerobic digestion; breakdown of organic waste into methane in the absence of oxygen. To read more about the project and track our progress, please visit the dedicated project website. Timeframe: 2013-2018.
6. Parasite-host interaction at the metabolic level
This project is funded by the Defence Science and Technology Laboratory (DSTL)
and is part of the partnership program between DSTL and University of Exeter. As an astonishing outcome
of antagonistic co-evolution, pathogens have evolved the capacity to interfere with the cellular
networks of their host. A major component of such “host reprogramming” targets host metabolism and
thereby results in improved pathogen growth. A particularly striking example of this is the ability
of several viruses to increase the rate of glycolysis in infected cells by up to 370%. More elaborate
modulations include, for example, the alteration of lipid and GTP biosynthesis. These findings
strongly indicate that a full understanding of host-pathogen interaction and pathogen-caused
disease states require a holistic view that considers host and the pathogen as a single system.
This system level analysis will be particularly valuable in the study of intracellular pathogens
and could lead to novel treatment approaches. Within this overall context, this project will
concentrate on the interaction of Burkholderia pseudomallei and Francisella tularensis with human
macrophages. Timeframe: 2012-2015.
5. Parasite disruption points in host networks
Funding for this PhD studentship comes from DSTL, under their research program on pathogens posing a biothreat. These and other parasites are documented
to have evolved elaborate molecular mechanisms to interfere with host cellular networks. pathways has emerged as a key mechanism that ensures parasites to
infect and reproduce in the host cell. This project will concentrate on F. tularensis and Burkholderia pseudomallei to (i) identify the interference points
of these parasites in the host networks, and (ii) understand the functional significance of such interference for the host. Timeframe: 2012-2015.
4. Deciphering The Molecular Basis of Environmental Persistence in Campylobacter Using a Systems Approach
Funded by BBSRC through the BBSRC/FSA/DEFRA joint Campylobacter research with industry call, this project is a collaborative effort between Prof. Rick Titball, Dr. Orkun Soyer, Dr. David Studholme and Dr. Olivia Champion.
Campylobacter jejuni (Cj) remains a leading cause of food borne infection in the UK with most cases arising from the ingestion of
contaminated poultry. Cj is able to survive unfavourable conditions such as antibiotic
treatment by forming metabolically inactive cells (persister cells). These cells serve as an environmental reservoir
and a source of infection, thus, a full understanding and control of food borne infection mediated by Cj requires an understanding of
the formation and regulation of the persister cell phenotype. We will undertake an integrated analysis of persister cell formation and
its molecular basis in Cj by combining our expertise in experimental characterisation of pathogenic bacteria and in evolutionary theoretical
analysis of bacterial behaviour at network level. This integrated, system-level evolutionary approach will identify the molecular basis
and evolution of persistence in Cj. Ultimately, this will enable us to design novel approaches towards reducing Cj levels
in the food chain and that are based on knowledge of the behaviour of the persister population in this bacterium. Timeframe: 2011-2014.
3. Evolving controllers and controlling evolution
Funded by the EPSRC, this project is a collaborative effort involving the labs of Dr. Orkun Soyer, Dr. Ozgur Akman and Prof. Declan Bates. It will combine tools and ideas from the fields of control theory and evolutionary theory to study specific molecular systems in order to derive evolutionary design principles underlying their robustness. In particular, we are interested in understanding which evolutionary conditions can result in the emergence of robustness in these systems and through what kinds of molecular or network-level mechanisms it is underpinned. We will then combine this evolutionary insight with in silico evolution approaches to design robust synthetic systems and engineering applications, in particular in aerospace control engineering. During the course of the project, we will also observe and analyze disciplinary transformations as they happen, not only from the point of view of engineering concepts making inroads into biology (the standard perception), but also from the perspective of biological concepts colonizing and reshaping engineering practices and principles. This aspect of the project will be run in collaboration with Dr. Maureen O'Malley and Dr. Sabina Leonelli. Timeframe: 2011-2014. EPSRC link
2. Engineering a semi-biotic immune system
This project is funded by the EPSRC Flashlight Funding: Engineering Challenges in Synthetic Biology initiative, which aims to support young academics that are the leaders of the future. This project is a collaborative effort involving six labs and aims to develop a semi-biotic immune device, which will detect and react to the early onset of pre- symptomatic disease in its host subject. At its core, the device will utilise a consortium of engineered bacteria, composed of a group of detectors that monitor the host for signals of disease onset (such as viral envelope proteins, tumour markers) and responders, that await signals from the detecting bacteria, before initiating the production and release of the relevant small molecule treatment. The engineered bacteria will be interfaced with traditional electronic components that oversee, record and transmit the status of the unit. Timeframe: 2010-2015. EPSRC link
1. Computational capabilities and underlying mechanisms in biological signaling networks
This project is funded by the prestigious Dorothy Hodgkin PhD Award. In this case Microsoft Research together with EPSRC will provide a full stipendum for the selected international student. The main aim of the proposed research is to analyze the relation between topological and biochemical features in signaling systems and response dynamics. The research strategy will involve building both detailed models of specific systems and generic models based on first-principles. Once such models are constructed we will be in a position to exhaustively analyze the repertoire of response dynamics in these systems and effectively map out their signal processing capabilities. Further, such models will allow us to analyze how different evolutionary processes can shape key features of signaling networks and generate novel information processing capabilities. Timeframe: 2010-2014.
Response dynamics and evolution in signalling networks regulating bacterial chemotaxis (PhD project, Munia Amin, funded by Exeter Systems Biology). 2010 - 2013.