A proteomics platform to enable next generation multidisciplinary bioscience
Lead Research Organisation:
Imperial College London
Department Name: Chemistry
Abstract
Life at the molecular level relies on proteins, long chains of amino acids which often fold into beautiful and functional 3-dimensional structures. Every cell in the body has its own particular mix of proteins, encoded by the genome, and adapted to the particular role of that cell - for example, immune cells produce proteins which can rapidly respond to infections, retinal cells produce receptors which enable us to detect light, whilst neurons produce proteins which enable transmission of extremely rapid signals to allow us to think and respond to stimuli. Other proteins are fundamental to the function of all cells, for example those which replicate our DNA and check it for errors, or ensure the correct separation of a cell into two daughter cells during cell division.
All proteins are further modified chemically, beyond the sequence encoded by the genome, by other proteins called enzymes, changing their structure in a way which enables their function. For example, modifications can be attached in response to a signal, or as a 'label' which tells other proteins in the cell to bind to it or degrade it, and the sequence can be 'shuffled' in various ways in a process termed alternative splicing.
These proteins are collectively termed the proteome, and can number over 10 million chemically distinct types in humans, with a range of abundance from 1 or 2 copies per cell up to millions of copies of a specific protein. The large majority of drug targets are proteins, and understanding how the proteome functions and is regulated, and its interactions with other molecules of life (DNA, RNA, lipids, metabolism, etc.) is one of the main goals of biology.
The study of this richly complex system is termed proteomics, and methods to identify and quantify the proteins in any sample - from single cells up to entire organisms - has become a cornerstone of modern science. The most important technology to achieve this is based on mass spectrometry, and recent innovations in this field now permit analysis of the proteome at the tiny scales present in single cells, as well as to comprehensively identify all the different forms of proteins, their complexes, and to assist with determining their 3D structures.
Our aim is to supplement currently obsolete proteomics equipment at Imperial College London with the latest proteomics equipment, to allow researchers to undertake world-leading collaborative science to understand the proteome in greater depth. These fundamental studies will accelerate impacts on society from medicine and clean energy to biorefining, agriculture and food security.
All proteins are further modified chemically, beyond the sequence encoded by the genome, by other proteins called enzymes, changing their structure in a way which enables their function. For example, modifications can be attached in response to a signal, or as a 'label' which tells other proteins in the cell to bind to it or degrade it, and the sequence can be 'shuffled' in various ways in a process termed alternative splicing.
These proteins are collectively termed the proteome, and can number over 10 million chemically distinct types in humans, with a range of abundance from 1 or 2 copies per cell up to millions of copies of a specific protein. The large majority of drug targets are proteins, and understanding how the proteome functions and is regulated, and its interactions with other molecules of life (DNA, RNA, lipids, metabolism, etc.) is one of the main goals of biology.
The study of this richly complex system is termed proteomics, and methods to identify and quantify the proteins in any sample - from single cells up to entire organisms - has become a cornerstone of modern science. The most important technology to achieve this is based on mass spectrometry, and recent innovations in this field now permit analysis of the proteome at the tiny scales present in single cells, as well as to comprehensively identify all the different forms of proteins, their complexes, and to assist with determining their 3D structures.
Our aim is to supplement currently obsolete proteomics equipment at Imperial College London with the latest proteomics equipment, to allow researchers to undertake world-leading collaborative science to understand the proteome in greater depth. These fundamental studies will accelerate impacts on society from medicine and clean energy to biorefining, agriculture and food security.
Technical Summary
Mass spectrometry (MS)-based proteomics is a critical technology in the biomolecular sciences, playing an essential role in discovery, quantification and characterisation of proteins, post-translational modifications and complexes. This technology finds diverse applications in support of fundamental cell biology, interactomics, structure determination, enzyme mechanism, small molecule ligand identification, membrane protein interactions, antibody and biological therapeutic characterisation, biomarker discovery, and many others. Analysis of tryptic peptides or intact proteins by high resolution mass spectrometry coupled to optimised high performance liquid chromatography is the proteomics gold standard, with platforms at the cutting edge now capable of identifying and quantifying proteins in single cells, up to samples derived from whole organisms.
We propose to establish a new multiuser proteomics facility open to all researchers at Imperial College, collaborating end-users in industry, and beyond, for the next 10-15 years, through acquisition of an Exploris 480/Vanquish NEO. This proteomics platform offers unmatched resolution and MS multiplexing capabilities alongside high sensitivity and throughput, enabling the widest possible range of applications to BBSRC-remit science in its class.
The only proteomics platforms currently at Imperial College are now effectively obsolete, suffering from poor sensitivity and low throughput. The capabilities of the new platform will thus enable a genuinely transformative range of new applications at Imperial, from single cell proteomics to deep time-resolved interactomics analyses, structural proteomics and proteoform analysis. This capability will immediately impact >£20M of BBSRC-funded research and training activity, and will ensure that proteomics capabilities at Imperial become internationally competitive for many years to come.
We propose to establish a new multiuser proteomics facility open to all researchers at Imperial College, collaborating end-users in industry, and beyond, for the next 10-15 years, through acquisition of an Exploris 480/Vanquish NEO. This proteomics platform offers unmatched resolution and MS multiplexing capabilities alongside high sensitivity and throughput, enabling the widest possible range of applications to BBSRC-remit science in its class.
The only proteomics platforms currently at Imperial College are now effectively obsolete, suffering from poor sensitivity and low throughput. The capabilities of the new platform will thus enable a genuinely transformative range of new applications at Imperial, from single cell proteomics to deep time-resolved interactomics analyses, structural proteomics and proteoform analysis. This capability will immediately impact >£20M of BBSRC-funded research and training activity, and will ensure that proteomics capabilities at Imperial become internationally competitive for many years to come.
