Plasmon-enhanced spectroscopy and imaging inside cells

Low sensitivity, fast photo-bleaching, photo-degradation and little chemical information are the bane of many biological studies and hamper our understanding of natural phenomena. Through the application of enhanced-spectroscopy techniques such as surface-enhanced fluorescence (SEF) and surface-enhanced (resonant) Raman scattering (SE(R)RS) these bottlenecks can be overcome. The enhancement can be achieved by employing special designer surfaces or nanoparticles of appropriate size, which act as antennae to trap impinging light and funnel it into molecules near the surface. This results in enhanced spectroscopic signals both in fluorescence (SEF) and Raman (SE(R)RS). Moreover, the latter technique has the power to resolve and identify many different molecules in a mixture. In the proposal, key component of cells called microtubules, which play an important role in cell division and, hence, are attractive cancer drug targets are used as the biological subject of investigation. The application of the proposed techniques seeks to find answers to important and enigmatic questions associated with microtubules and in the process prove the benefits of the proposed techniques over conventional spectroscopy & imaging methods. Further, we will study the interaction of a common chemotherapeutic drug with microtubules inside cells. Besides understanding the mechanism of action this in turn could lead to efficient application of drug dosage regimes, less side effects and reduced costs for therapy. Overall, the proposed research will pave the way for application of enhanced-spectroscopic techniques for targeted biological studies and functional imaging and thus establish a new paradigm in biological research.

Apart from academic beneficiaries (contained in separate document) there will be many in the wide public domain that will benefit from the research proposed under this fellowship. In particular, I have strong links with D3 technologies (a subsidiary of Renishaw Plc, a leading Raman equipment supplier) who have commercialized a nanostructured SERS transducer. They I am sure they will benefit from the research and will be keen in using the SEF technology being proposed with their substrates. Biacore Life Sciences (owned by GE) are also engaged in detection technologies and will be interested and also benefit from the research. Pharmaceutical sector will be interested in the research proposed her and in particular, industry engaged in drug discovery and screening could be beneficiaries in the long term. As detailed elsewhere the results can be easily extended to monitor pesticides, weed killers, toxins and even environmental pollutants etc. and therefore could be of benefit to agriculture, public health and hygiene. The methodology proposed here also could be utilized for forensic analysis. Hence, not only the private sector but also the public sector such as DSTL might be interested in harnessing these offshoots of current research. As also mentioned in the case of support, the research proposed here as two complementary impacts that is in advancing current scientific understanding and the other much wider technological significance. The research will be a huge technical advance for bio-imaging and understanding biology and hence have the potential to impact global research. Some of the techniques proposed (such as SEF) are not yet employed much in the UK. Therefore, the project will ultimately result in enhancing the country's competitiveness, and can also lead to wealth creation. The benefits of the research besides increasing creative output across many disciplines, in particular biology. It has the potential to aid drug research such as developing Cancer therapies by increased understanding and new drug testing regimens, faster discovery with low side effects. All of this will enhance health and quality of life of people. In my view with continued funding support many of the benefits can be realized in a 5 to 10 year timescale. Besides sharing and exchanging scientific information through publication in research journals and presentations at conferences we will strive to communicate with prospective industrial partners and collaborators. Intellectual property (IP) generated will handled through the technology transfer office of the University. The University of Cambridge has been carrying out knowledge and technology transfer since the early 1970's and this function is currently performed by Cambridge Enterprise Ltd (CE), wholly owned subsidiary of the University formed in December 2006. Cambridge Enterprise consists of three overlapping business units; Technology Transfer, responsible for working with inventors to evaluate, protect, market and licence intellectual property. Consultancy services; providing support for Cambridge staff and research groups wishing to provide consultancy services to third parties. Seed Funds and Venture Services that work with prospective entrepreneurs to provide access to capital and business expertise. These three business units, together, will provide a comprehensive range of services for identification, protection and exploitation of research results.