Background
Bioinformatics is the set of tools that are available to interrogate and and prise information from worldwide databases on annotated sequences, expression profiles and structures. Leading bioinformatics centres, such as the NCBI in Bethesda, USA, and the EBI in Hinxton, UK, maintain the databases and develop the software tools to interrogate them. In UVS we are providing the links to the leading bioinformatics centres and we are offering the expertise to use the links and the databases in the most effective ways. To a limited extent, we are also maintaining local mirror images of the databases and developing specific software tools to serve specific projects. This activity was initially set up within the Telethon Institute of Genetics and Medicine in San Raffaele, has been working for the last 6 years, and has now been subsumed within UVS.
Functional genomics is the coordinated exploration of biological functions at whole-genome level. Most of the exploration at the level of sequences are now part of routine bioinformatics approaches. The analysis of the the expression profile of genes in cells, tissues or organs in physiological and/or pathological conditions is now the next frontier. Expression profiling is currently done by high density microarray technology. Target sequences are immobilised on solid supports (membranes or glass) and are hybridized to ensembles of fluorescently labelled cDNAs obtained by reverse transcription from mRNAs extracted from the biological material. The intensity of fluorescence from each individual target is related to the abundance of the mRNA in the biological sample.
Microarray technology is currently present in UVS as a partnership with IFOM in Milano. This gives us access to 25 000 human Unigene clones (each of which is a bona fide expressed gene ok known sequence). This collection is physically present in UVS and is ordered.
We plan to organise a Microarray Core Facility and Bioinformatics service (MCFB), that should provide a spotting service on the solid supports, hybridization to investigator-provided cDNA preparations, and reading and analysis of the hybridization signals. The technical details of the system that will be chosen have not been finalized (see following sections), but we reckon that this service will be essential for the support of most research lines in UVS.
Bioinformatics and expression profiling orient the investigator to the understanding of the function of specific genes, but in most cases do not provide definitive prove of their function within cells or organisms. Much more defined information can be gathered by perturbing the expression of the same (or orthologous) genes within the context of a whole mouse. This is done by directed mutagenesis of the mouse, either by constructing transgenics or knockouts.
