NextGen Sciences Ltd of Huntingdon, Cytomyx plc and Dr Carlos Caldas MD, a researcher at the University of Cambridge and holder of grants from the Cancer Research Campaign, has announced the formation of a three-year programme to develop a series of protein biochips for analysis of breast cancer.
LINK Applied Genomics award will help fund breast cancer research
The project is part funded by an award from the LINK Programme in Applied Genomics sponsored by the Department of Trade & Industry (DTI), Biological and Biotechnology Sciences Research Council (BBSRC) and MRC.
As a result of this initiative, the University will gain access to a new proteomics technology, NextGen will develop a range of breast cancer protein biochips as well as its high throughput automated protein expression Protein Library Management System (PLMS) and Cytomyx will build a valuable repository of clones for use in genomic and proteomics based drug discovery.
'My research group has been studying breast cancer at the gene and gene transcript (mRNA) levels using human biopsy cell lines as well as primary tumours with linked appropriately anonymised clinical information,' explained Dr Caldas.
'The research data is being assembled into a relational database, tracking and recording all information generated at the gene copy and mRNA expression level using DNA arrays and relating this to relevant clinical information. This initiative with NextGen and Cytomyx allows us to access new technology in protein expression analysis and to combine this with the genomics and transcriptomics information we are already gathering. Our aim is to make the database and the bioinformatics tools we develop, freely available to the research community.'
Through this collaboration, the University of Cambridge, NextGen and Cytomyx will define a series of key proteins involved in the disease process.
'We need to identify a series of proteins which, while they may or may not be causative or suitable as 'drugable' targets, act as metabolic indicators of disease status. As we understand the dynamics, we can use the human cell lines as disease process models and develop a whole-cell screen for drugs that act on these cells to slow or stop their growth.' said Dr Caldas.
'A method where these key protein markers can be analysed is vital to understanding the disease and another objective of this initiative is to generate tools that my laboratory needs to analyse human tissue and cell lines from the clinic.'
'A central aim of this initiative is to create prototype protein biochips tailored for this research,' explained Dr Linda Cammish, Director of Business Development at NextGen and overall programme co-ordinator.
'NextGen has developed new technologies in high throughput protein expression analysis using protein biochips including novel protein immobilisation technologies and a microfluidics system for high throughput protein expression analysis.
'We are very pleased to work with Dr Caldas on this programme and envisage this collaboration will allow us to not only develop breast cancer related protein biochips that can be used globally by researchers in this field but also provide a demonstrable example of how protein biochips can be used for clinically relevant studies with human tissue.'
'Using the NextGen proprietary technology we can attach antibodies, antibody fragments or phage molecules to the surface of a novel protein biochip matrix that NextGen has developed in collaboration with Nunc A/S, Denmark,' explained Dr Cammish.
'The resulting biochips can be used to determine expression profiles in complex protein matrices. It is important to validate each antibody against its corresponding antigen prior to inclusion onto the biochip and to do this we need to create high density antigen arrays on a protein biochip to assess the affinity and specificity of the antibodies of interest.
'For this purpose at least 1,000 full length genes cloned in the right reading frame and confirmed by DNA sequencing are required and, due to their expertise and capacity to undertake cloning and sequencing operations, Cytomyx is the ideal partner for this initiative.'
As part of this collaboration, Cytomyx will clone full-length genes from the collection of cDNA libraries that the company has developed. 'We have built this library collection, which contain most of the genes from the human genome, over several years,' explained Mr Mike Kerins, Chief Executive Officer of Cytomyx.
'To date, we have used this resource for our service programmes with biopharmaceutical companies however we intend to extend the value of our current technologies through partnerships that provide us with early access to key technologies of the future and therefore use of this resource for programmes such as this initiative with the University of Cambridge and NextGen is an important element of our business.
'We will be cloning the genes identified as relevant to this initiative and will make these clones and the corresponding proteins available to our partners in ways that enable their discovery research.'
The clones generated and qualified by Cytomyx will be transferred to NextGen where the genes will be subcloned into a series of novel, proprietary vectors and the targeted proteins expressed in a range of hosts to create a protein library exhibiting relevant molecular diversity and suitable for direct attachment onto the biochip surface.
'This is a major undertaking for NextGen requiring factory-like processes and advanced automation,' said Dr Kevin Auton, Chief Executive Officer at NextGen.
'To do this we have developed a series of high throughput protocols suitable for systematic protein expression and have begun to automate each step. This initiative will enable us to extend our capacity to automate the whole process by piloting our PLMS, which is a suite of automation allowing subcloning and transfection of a gene library into a series of expression hosts and further automation to retrieve, grow cells under multiple conditions and harvest the recombinant proteins in a massively parallel process using technology developed at NextGen.'
'The DTI and the BBSRC are delighted to support these three organisations in this impressive endeavour,' said Dr Caulcott, the LINK Applied Genomics Programme co-ordinator.
'The project underwent extensive review by a panel of experts from academia and industry as well as considerable critique from the DTI before the award was granted. The collaboration between a world-class academic researcher such as Dr Caldas and the two commercial parties, NextGen and Cytomyx, is exactly the type of project the Applied Genomics Programme encourages in assisting UK scientists and companies to exploit the wealth of expertise that the UK has established as a result of the Human Genome Project.'
Under the LINK Applied Genomics programme, DTI awarded grants of up to 425,000 and 134,000 to NextGen and Cytomyx respectively and the University of Cambridge received a grant of 310,000 from BBSRC.
Dr Linda Cammish, Project Programme Co-ordinator and Director of Business Development, NextGen Sciences Ltd,
t: +44 (0) 1480 410 856 f : +44 (0) 1480 410 858
Beck Lockwood, The University of Cambridge, Press and Publications Office,
tel: +44 (0) 1223 332300, fax: +44 (0) 1223 330262
Mr Mike Kerins, Chief Executive Officer, Cytomyx plc,
tel: +44 (0) 1223 508191, fax: +44 (0) 1223 508198,
email: firstname.lastname@example.org, www.cytomyx.com
LINK Applied Genomics programme website: www.appgen.org.uk