Molecules, Cells and Systems
Across the partner institutions we have an enormous breadth of internationally recognised excellence in bioscience research ranging from single molecule to whole organism and ecosystem studies. MIBTP will focus on those areas of fundamental research, predominantly in molecular biosciences, that use quantitative and modelling approaches and have the strongest BBSRC support. 20 studentships will be funded in these areas each year.
Our work on systems modelling of the regulation of gene expression has global impact and substantial funding resource. There is excellence ranging from the influence of DNA-associated proteins on prokaryotic genome organization (Grainger), epigenetics (Gutierrez-Marcos) and chromatin structure and function (Cowley, Ntoukakis), through the interactions of specific and global transcription factors with the transcriptional complex (Bonifer, Busby, Schwabe, Carr, Hebenstreit), to RNA splicing (Dominguez), and to the control of translation by intrinsic and external molecular signals (McCarthy, Willis, Bushell). Linked are the state-of-the-art structural investigations by NMR, X-ray crystallography and other biophysical approaches giving resolution of expression processes at the atomic level (Carr, Dominguez, Schwabe), and -omics technologies to quantify reactions to environmental prompts (Falciani, Rand, Viant). Biophysical, biochemical and genetic data feed into systems models to define key steps and quantify each level of control (McCarthy, Hebenstreit). We have expertise on modelling gene regulatory networks in both prokaryotes and eukaryotes (Denby, Henderson, Drea).
Internal clocks influence patterns of behaviour. Startling new components have been predicted as a result of systems modeling of gene networks underlying circadian oscillators in both animals and plants (Carre, Finkenstadt, Rand, Ott). Work on the molecular details of biological clocks in insects (Drosophila), crustaceans (krill), mammals (mouse), (Kyriacou, Rosato, Tauber) and plants (Carre) help us understand how clock neurons are organized and how circadian information flows through the network.
Elucidating the molecular mechanisms that coordinate and execute cellular processes is another core activity across all three institutions and there has been substantial investment in systems technologies including quantitative (phosphor-)proteomics, transgenics and imaging facilities with associated data analysis tools, to provide a world class support infra-structure. The Core Biotechnology Services (UoL) and Centre for Mechanochemical Cell Biology (UoW) and Birmingham Advanced Light Microscopy centre have sophisticated microscope systems for techniques from live-cell imaging to single molecule mechanical recordings.
Molecular research addresses G-protein coupled receptors (Tobin, Challiss, Evans R, Ladds, Overduin, Rand, Wheatley) and the protein phosphorylation networks which control cell growth and mitotic and meiotic divisions through the MAP-kinase (Pritchard) and NEK-kinase (Fry) pathways); global approaches are being applied to unravel the regulatory circuits of important microbes including the phospho-proteome of the malaria parasite (Tobin), and the control systems of acinetobacter (O’Hare) and the tuberculosis bacterium (Mukamolova). Related studies use Systems Biology to unravel signaling mechanisms and model how cells respond to external stimuli; key areas of active research use modelling studies to investigate G-protein signalling in yeast and mammalian cells (Ladds, Rand), response of the human NRF transcription factor to different nutrient treatments (Thornalley, Rand), and the dynamics and function of the NF-kB signaling system (Rand, Ott).
Other exciting related research investigates the biophysical and cell-biological mechanisms that respond to these signalling systems to control motorised self organisation in cells; this includes studies of the molecular motors of microtubules, chromosome segregation and cell migration (Arumugam, Bretschneider, Burroughs, Cross, McAinsh, Rappoport).
Neuroscience is vibrant across many departments at each institution with internationally competitive experimental and theoretical research ranging from the subcellular to the cognitive level. The power of developing novel biosensors is realized by spin-out company successes (Sarissa Ltd) as well as by their application to purine communication in CO2 sensing in animals and hormones in plants (Dale). Neuro-glial interactions (Hidalgo and Pankratov), synaptic plasticity in learning and stress (Forsythe, Frenguelli, Hartell) and neural control of blood flow (Marshall) underpin organism level research on cognition, behavior and communication (Kita), motor learning and coordination (Miall, Reynolds), imaging and mapping neural processes (Kourtzi, Welchman), conscious perception (Quian-Quiroga), and information processing during adaptive behaviour of locusts (Matheson, BBSRC Fellowship). These are complemented by the work on circadian clock systems (above) and neuronal circuitry development in zebra-fish (McDearmid).
Synthetic biology is the design and construction of novel biologically based parts, devices and systems, as well as the redesign of existing natural biological systems for useful purposes. Synthetic Biology expertise within the partnership ranges from bionanotechnology (Preece, Dafforn, Jaramillo), gene circuits (Busby, Bates), metabolic engineering (Challis, Thomas, Corre), engineering microbial communities (Soyer, Asally). Synthetic biology projects can also be found in Food Security and Industrial Biotechnology.