Manchester Chemical Biology Network

Chemical biology is the area of science at the interface between chemistry and biology, which uses chemical tools including structural, physical and analytical methodologies as well as synthetic small molecules to gain deeper insight into the function and properties of biomolecules and biomolecular systems (cells). Whilst great benefit can be derived from such interdisciplinary research, particularly in the area of healthcare, boundaries that exist between traditional disciplines have hindered the progress of chemical biology in the UK. In 2006, the University of Manchester took the lead in addressing this issue by establishing the Manchester Interdiscplinary Biocentre (MIB), which was the first major university institute in the UK to bring chemists and biologists together to do research in the same building (ca. 300 in total). We propose to build on this solid foundation, using MIB as a focal point and meeting place, to develop a much wider chemical biology network that unites scientists from across the university including researchers in medical science who can further develop research in chemical biology for medical applications. Importantly, the new Manchester Chemical Biology Network (MCBN) will include partners and collaborators from the pharmaceutical and biotechnology industry, knowledge transfer networks, healthcare providers and medical charities. These end users of chemical biology will help guide the direction of the research in the network and enable us to establish critical cross-discplinary collaborations. Increasing the effectiveness of our collaborations with the end users will be essential if we are to see maximum benefit derived from this research. Ultimately this could include new approaches for the treatment of human disease ranging from bacterial infections through to cancer.

To enable maximum impact from our research to be realised, the network will focus on several key themes. The first theme, small molecules and chemical tools, will involve the development and application computational based approaches for drug design and virtual screening. Such activities can help identify potential drug candidates, which we will synthesise. Also many pharmacologically active small molecules are derived from natural sources (plants, soil bacteria and marine organisms). We will produce and modify these natural product leads using synthetic and biosynthetic methods. In the second theme, new concepts in target modulation will be developed including array based technologies for screening potential drug targets, where targets (proteins or oligosaccharides etc.) are attached to surfaces allowing high throughput imaging of their interactions with other cellular molecules including drugs. Crystallography and NMR methods, developed in Manchester, along with other physical methods will be applied to probe the structure and dynamics of cellular targets, which can further help in the design and optimisation of lead molecules for therapeutic applications. We will apply our knowledge of enzymology (how enzymes work) and cell biology (how the complex components of human cells interact) to uncover new enzymes, other biomolecular targets and pathways for therapeutic intervention, which we will interrogate with our arsenal of small molecules etc. In the third theme, target deconvolution, we will take a systems biology approach, which models all the components in the cell and allows the broader response of cells to abiotic substances (e.g. drugs) to be interpreted. This can be particularly important for predicting possible toxic (side) effects of drugs. In the final theme, intersection of large and small molecules, we will develop new methods for improving the properties of proteins and antibodies for use as therapeutic agents (biopharmaceuticals). We will also develop new drug delivery systems using nanoparticles and other smart materials programmed to target and release drugs in specific diseased cells, but not healthy cells.

The MCBN will establish a unique platform to explore advances in chemical biology and their potential application across the biological and medical sciences. In addition, it will allow the development of innovative approaches to biological problems, provide a forum for exchange of best practice and expertise and allow collaborations to form solid sustainable links towards translational research with accelerated impact. Indeed, it is vital that translation of fundamental advances in chemical biology through to cell biologists, pharmacists and medics is possible to enable better drug design, identification of drug targets, optimisation of small molecule drug candidates through to biopharmaceuticals, and thus impact on human health. Whilst the healthcare grand challenge will be the main impetus for our research, some of the basic methodologies and technologies we develop could also be applied in the animal healthcare and agrochemicals area.

In addition to the obvious benefits to the academic community within the University of Manchester, nationally and internationally, the network will work closely with its industrial members to ensure knowledge transfer and commercial exploitation. This close industrial relationship of the network with companies from across the field including large pharmaceutical companies may impact on not only the nation's health, but also could contribute to wealth creation and economic competitiveness in the UK. The network will form a very strong cross disciplinary body that with its communication with non-government and government organisations will be in a position to influence scientific policy and reach out across the wider community through public engagement.

The network will form a strong basis for further collaborations and provide a unique opportunity to seed fund exchanges of expertise and personnel, explore proof of concept research and gather preliminary data. As such the full impact of the network may not be realised during the initial two year funding but will develop through stronger collaborations and development of full research projects. Results from collaborative projects will result in joint research publications in high quality peer-reviewed journals and will be presented at local, national and international conferences where appropriate. Exploitation of findings will be further enhanced by seeking follow-on funding to develop proof of principle, or biological application, in order to develop expertise to answer specific biological/medical problems.

The network will be expected to contribute significantly to the field of chemical biology and encourage an ethos of cross-disciplinary research. In addition to scientific advances, the network will spread an ethos of cross disciplinary networking and provide an unique opportunity for our research community to gain a better understanding of the industrial sector vital for development of transferable skills and their personal and professional training and development.