The Computational and Chemical Biology of the Stem Cell Niche

Stem cells in tissue exist within a specialist environment termed the "niche".
The niche ("the soil") that surrounds stem/progenitor cells ("the seed") in developing or damaged organs has a profound effect upon the behavior of the stem cells.
The focus of this application is to bring together stem cell researchers together with chemists to synthesize artificial niches that will enable stem cell to: (1) grow in a more efficient and controlled manner (2) be differentiated into functioning cells that could be used to repair damaged tissue. This project will produce large amounts of data and so to efficiently capture and analyse all this data we will collaborate actively with experts in the handling and analysis of such large amounts of data - bioinformaticians.
This facility will be available to all stem cell and regenerative medicine researchers throughout the UK at minimal cost to help the UK regenerative medicine community as a whole to rapidly develop new stem cell based and regenerative therapies for patients. We envisage the creation of implantable artificial niches that will control and guide the development of replacement issues from stem cells.

UKRMP Centre for The Computational and Chemical Biology of the Niche (CCBN)
The resource requested is the use of MRC funds to i) immediately fit out of existing "shelled" space to create a dry-lab Computational and Chemical Biology Centre for stem cell niche analysis within the Systems Medicine building at the Institute of Genetics and Molecular Medicine (IGMM) and ii) purchase the equipment required to upgrade our existing facilities for next-generation Chemistry, together with the construction using matched University funds of iii) a dedicated wet-lab facility for niche Chemistry as an extension of the SCRM building that houses the MRC-CRM and the newly created UKRMP Hub for engineering and exploiting the stem cell niche.
These facilities will function as a "research hotel" for the UK stem cell and regenerative medicine community. Visiting researchers will occupy dry-computational and/or wet lab space for a period of time, with minimal barriers, to develop their particular cell/niche activity, thereby maximising the national strategic value of the investment and accelerating the translation of regenerative medicines.

Regenerating damaged tissues and restoring their function is one of the major goals of biomedicine. Diseases that cause tissue degeneration and injury present a huge and ever-increasing clinical burden, in the UK costing the NHS well over £1 bn/year, with musculoskeletal disease alone accounting for 8.8 million UK working days lost/annum.

The Centre for Computational and Chemical Biology of the Niche will bring together experts I stem cell biology/regenerative medicine with chemists and bioinformaticians and thereby expedite stem/progenitor cell discoveries and translate these finding to the clinic. We will achieve this by determining how local tissue niche composition directs stem cell phenotype, growth and differentiation. By creating niche-based biomaterial platforms for tissue-specific engraftment and regulation of cell phenotype we will be able to develop regenerative artificial niches for patients with hitherto untreatable diseases.

We will utilise high throughput, high content and phenotype screens to fast track achievement of these key goals. The bringing together of these 3 separate disciplines has the potential to boost regenerative medicine research worldwide. By promoting this facility as a "research hotel" for the UK wide stem cell and regenerative medicine community we will maximise the impact of this capital investment. By drawing upon internationally recognised strengths in extracellular signals in the niche direct cell behavior and phenotype and their ability to repair tissues, allowing us to address directly the well-recognised need to understand and exploit the cellular microenvironment to drive effective tissue regeneration.
To engage with UK and international bio-medical communities, we will use the data sharing, networking and, teleconferences and workshops of the existing UKRMP hubs. By having meetings open to hub members, national (UKRMP hub) and international colleagues, this will strengthen the UK standing in international stem cell research.

We will participate at a high level in major national and international conferences where we will report our scientific discoveries and translational advances; disseminate our data in high-impact scientific journals, thus contributing prominently to the development of a world-leading UK 'brand' in tissue regeneration and repair.

The Centre for Computational and Chemical Biology of the Niche will be of interest to industry, e.g. in the development of niche-based products and tools such as stem cell selection systems, marker arrays, lineage pathway inducers, natural epitope-derived bio-materials and extra-cellular matrix products. Our University has a strong records of exploiting innovative research findings through commercialisation of intellectual property (now through Edinburgh BioQuarter). Outputs for exploitation may include licensing of cellular and extra-cellular matrix reagents/biologics and protocols, in-house assays/technologies, co-development of technologies licensing of IP, consultancies.