the group's research

RESEARCH
 

These paragraphs are not necessarily regularly updated - if you want to know what I'm planning next check the section on the left or come and talk to me (safer option)!
Complete references for the papers mentioned below can be found under the PUBLICATIONS tab.
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  • Regulation of gene expression in health and disease

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  • The biggest surprise from studying the human genome is the versatility of RNA as a regulator of gene expression. The realisation that RNA is potentially controlling as many or more regulatory events than proteins do has made the field of bioinformatics a truly exciting place to be at the moment: relatively little is known about RNA and a wealth of data out there are prime for computational analysis.
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  • We are already active in two areas involving regulation of gene expression: a) Autism (PhD student Krzysztof Szkop), where we are interested in exploring areas of the genome that have so far been mostly ignored by researchers in the area, and b) the RNA targets of FMRP, a protein implicated in mental retardation and other cognitive deficits (MSc student Andrejus Abrosimovas). We are starting to explore publicly available next-generation sequencing data (RNAseq) and would be very keen to collaborate with labs that share our interests and produce such data.
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  • One of the group's long-standing interests are in understanding and predicting riboswitches using computational methods (MSc students: Paul Golby, Joe Southan). We are also developing collaborations with experimental groups interested in non-coding RNAs and projects in this area will appear as rotation/PhD students in the ISMB PhD programmes (eg riboswitches and other regulatory RNAs in mycobacteria in collaboration with Dr Tine Arnvig, UCL).
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  • Finally, the group was also involved in computational work that assisted structural, biochemical and biophysical studies of RNA-binding proteins, especially the Kaposi's sarcoma associated herpes virus (KSHV) proteins implicated in host shut-off/mRNA decay (PhD student Anathe Patschull under the primary supervision of Dr Tracey Barrett).
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  • Protein-small molecule and protein-protein interactions

  • The group has a long history of applying computational methods (mainly docking) to identify promising leads in drug design projects, or ligands relevant to protein function.
  • One of our longer-running projects is in the area of predicting the druggability of protein-protein interactions. The group (Paul Ashford, in collaboration with Dr Mark Williams and Prof. David Moss) has developed a method for easy visualisation of conservation and variability of surface pockets across varied ensembles of protein conformers. These have the potential to reveal potential allosteric sites that could be targeted. This work was part-funded by Pfizer.
  • Reference: Ashford et al. (2012).
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  • In collaboration with experimental groups we are carrying out docking projects relating to either drug design or protein function. We have worked with alpha1-antitrypsin (PhD students Anathe Patschull and Florence Thomas, co-supervised by Dr Bibek Gooptu), the resuscitation promoting factor B from M. tuberculosis (PhD student Anna Heddell, co- supervised by Prof. Nick Keep), insect odorant-binding proteins (Prof. Nick Keep), murE from M. tuberculosis (PhD student Juan Guzman, PI: Dr Sanjib Bhakta) and more recently sodium channels (in collaboration with Prof. Bonnie Wallace).
  • References: Patschull et al. (2012), Patschull, Segu et al. (2011), Chang et al. (2011), Guzman et al. (2011), Gooptu et al. (2009).
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  • We are particularly interested in fragment-based approaches and have recently collaborated with researchers from the Istituto Italiano di Technologia on a project that led to the creation of SERAPhiC, a high-quality dataset of protein-fragment crystal structures from the PDB that can be used as a benchmark for the development of new software and scoring functions for the prediction of protein-fragment interactions. We are also currently developing software for analysing the interactions between ligand fragments and protein environments (MSc student Christian Spiteri, 2011).
  • Reference: Favia et al. (2011).
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  • In the past we have been interested in the origin and mechanisms of binding and catalytic promiscuity. We are currently attempting to construct predictive computational models of the ligand-binding promiscuity of proteins (Undergraduate student Krzysztof Szkop, PhD student Benjy Lichman and MSc student Bojan Cvijan, in collaboration with Professor David Moss). We are also just starting a collaboration with Prof. Brian Henderson and Dr Andrew Martin in the area of moonlighting proteins (PhD student Florence Thomas).
  • References: Nobeli et al. (2009), Macchiarulo et al. (2004).
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  • The metabolome and metabolic pathways

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  • We have a long-standing interest in the analysis of the collections of endogenous metabolites in model organisms from a structural and physicochemical point of view. We use chemoinformatics methods to reveal the relationships between metabolites within a species, compare metabolites from different species, and finally compare endogenous metabolites to exogenous (human made or environmental) small molecules.
  • References: Macchiarulo et al. (2009), Bashton et al. (2009), Bashton et al. (2006), Nobeli & Thornton (2006), Nobeli et al. (2003).
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  • In collaboration with Dr Adrian Shepherd (BBK), we are exploring the reliability of homology-based metabolic pathway reconstructions (Jan Czarnecki, PhD student). Jan is also developing text mining software for extracting information from the literature that could be used to validate and enrich metabolic networks. His studentship is part-funded by Unilever.
  • Reference: Czarnecki et al. (2012).
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  • We are currently building a collaboration in the area of medical informatics that will involve the analysis of metabolomics data using knowledge of metabolic pathways. Watch this space!
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