High Resolution Mass Spectrometer to support Proteomic Research across the Southern 4 Proteomic Consortium

New instrumentation for increased capability in Proteomic Research

Proteins are a major building block of cells and perform a huge range of biological functions. Proteomics is the systematic study of the expression, functions and interactions of proteins.

The key techniques used in proteomics are mass spectrometry (MS) and liquid chromatography and are performed on instruments called Mass Spectrometers; and High Performance Liquid Chromatography (HPLC) systems. In combination, these two instruments are designed to separate and identify proteins, fragments of proteins (peptides) and modified proteins obtained from cells, tissues and biofluids. They allow us to compare the amounts of proteins between different conditions (e.g., comparison of protein levels between normal cells and cancer cells), and to identify proteins important within a specific biological process including normal ones and those important in human diseases. This application will support the purchase of an advanced Mass Spectrometer and HPLC system with an enhanced ability to measure the amounts of these proteins and peptides at very low levels and with high accuracy.

The instrumentation has been requested by the Southern 4 Proteomic Consortium and will form part of a Proteomics hub in the South of England that will allow several universities to use this state-of-the-art instrumentation. This consortium also provides a forum to exchange proteomic expertise and knowledge; and to train researchers in the latest proteomic techniques. Housed within the Centre for Proteomic Research at the University of Southampton, the increased capacity and advanced capabilities of this instrumentation will permit a wide range of proteomic studies within areas of strategic importance, including those within many BBSRC priority areas including healthy aging across the lifecourse; bioenergy, generating new replacement fuels for a greener, sustainable future; food, nutrition and health; sustainability enhancing agricultural production; systems approaches to the biosciences; synthetic biology and data-driven biology.

Proteins are the ultimate effectors of almost all cellular processes. As such, there is a requirement for biological systems to be explained in terms of the levels, interactions, regulation and modifications of proteins - which are the capabilities of proteomics. The requested instruments are a new high-resolution hybrid Mass Spectrometer (MS) and nanoscale Ultra High Performance Liquid Chromatography system to support cutting-edge proteomic research across multiple institutions in the South of England as part of a Southern Proteomics Consortium (S4PC).

This state-of-the-art instrumentation will provide a step-change in Proteomic research, allowing investigators to perform in-depth and innovative proteomic studies regardless of the biological system under investigation, bringing an increase in both capability and capacity to perform large-scale experiments using label-free and stable isotope-labelling strategies, provide sensitive targeted quantitative proteomics and a substantially improved ability to characterize post-translational modifications. These new capabilities will allow researchers to tackle important new research questions, many of which are within the BBSRCs strategic priority areas. Importantly, the latest generation of MS instruments has improved performance characteristics (enhanced mass accuracy, resolution, modes of acquisition and sensitivity), which will increase both the quality and quantity of proteomic data that can be obtained. This investment will also have a major impact on the proteomic technology that our external academic and industrial collaborators of the S4PC institutions have access to, extending the range and quality of research that can be performed.

The requested instrumentation will provide proteomic capability to researchers across the Southern 4 Proteomics Consortium with applicants representing academic departments in Biosciences, Oceanography, Chemistry; and Health and Medical Sciences, illustrating the broad impact of the research proposed. The new instrumentation will also provide ample opportunities for strengthening current collaborations and forging new links with other institutions and industry.

The research proposed is relevant to important world issues such as environmental change, food security, bioenergy, healthy ageing, as well as providing high-class bioscience underpinning many important health-care issues. The work undertaken in the individual projects will also have impact within those research areas.

C. Proud's research is important for academic researchers and industrial partners, who are interested in eEF2K or the Mnks as therapeutic targets in diseases such as cancers. A better knowledge of the normal functions of these kinases and pathways will aid understanding of their roles in animal physiology and healthy ageing, thus ultimately benefiting the pharmaceutical industry, the healthcare sector and the wider community.

M. Terry's research focuses on how the photosynthetic apparatus in plants is assembled in the early stages of seedling development. This research will benefit those working in the areas of chloroplast-nucleus signaling/biogenesis, photosynthesis, and stress signaling. It is relevant to industrial partners/other organizations designing crop plants to increase productivity and the wider public as it addresses important issues related to the food security/bioenergy debate.

R. Ewing's research focuses on identifying new interacting proteins in signaling complexes or networks that are rewired in disease. This research will benefit researchers interested in interaction proteomics and signal transduction pathways, particularly in cancer, an important factor in the ageing population, as well as industrial partners interested in new therapeutic targets, the healthcare sector, patient communities and the wider public, where cancer can have a major impact on their lives.

T. Bibby's research is focused on the ability to engineer photosynthetic cells from marine algae to maximise their energy efficiency for conversion into useful biofuels/bioproducts. This research is therefore important for academics and industry interested in using marine algae for synthetic biology and bioenergy research.

R. Cramer Medicinal plants and their natural products are a potent source of new drug compounds and disease therapies. Novel data revealing location-specific protein expression in an important medicinal plant provides essential information for elucidation and isolation of medically and economically valuable plant metabolites. These are of major interest to the pharmaceutical industry, the healthcare sector and the wider public.

B. Moore's research focuses on the mechanisms involved in lipid loading in human hepatocytes. Disruption of nutrient metabolism and energy homeostasis in the liver leads to conditions such as obesity and type 2 diabetes, all of which prevent healthy aging. The identification of rationalised strategies to protect the liver from fat accumulation would be of major interest to the Foods and Pharmaceutical industry and have a huge impact on the public health and well-being of the UK population, and would in the longer term reduce the cost burden of UK healthcare.

G. Kneale's research into R-M controller proteins will advance our understanding of the fundamental mechanisms of gene regulation in bacteria, and provide new insights into novel mechanisms of DNA sequence recognition by gene regulatory proteins. An understanding of these mechanisms will be benefit medical microbiologists and the pharmaceutical industry in providing new targets for novel anti-bacterial drug development.