Mass Spectrometry

International audienceFor twenty years or so now, mass spectrometry has been used to get exact measurements of the mass of biological molecules such as proteins, nucleic acids,oligosaccharides, and so on. Over the past ten years, this technology has followed the trend toward miniaturisation and the samples required can be much smaller. In particular, the nanoelectrospray source (online or by needle) allow one to work at flow rates of a few tens of nanolitres/min. There are many applications, both in the field of proteomics and in the analysis of protein structure, dynamics, and interactions. Combining this source with nanoHPLC, complex mixtures only available in small quantities can be separated and analysed online. There are also some advantages over conventional HPLC, despite a set of constraints related to the small dimensions and low flow rates. Combining capillary electrophoresis with the electrospray source also gives useful results, with its own set of advantages and constraints. Finally, developments are currently underway to combine this source with chips, providing a means of separation and analysis online

Bypassing cellular senescence by genetic screening tools

8 páginas, figuras.Bypassing cellular senescence is a prerequisite step in the tumorigenic transformation. It has long been known that loss of a key tumour suppressor gene, such as p53 or pRB, is necessary but not sufficient for spontaneous cellular immortalisation. Therefore, there must be additional mutations and/or epigenetic alterations required for immortalisation to occur. Early work on these processes included somatic-cell genetic studies to estimate the number of senescence genes and nowadays are completed by in vivo models and with the requirements to bypass senescence induced by oncogenic transformation in stem cells. These principal studies laid the foundation for the field of senescence/immortalisation but were labour intensive and the results were somewhat limited. Using retroviral-based functional genetic screening, we and others identified universal genes regulating senescence/immortalisation (either by gain or loss of function) and found that some of these genes are widely altered in human tumours. We also explored the molecular mechanisms throughout these genes that regulate senescence and established the causality of the genetic alteration in tumorigenesis. The identification of genes and pathways regulating senescence/immortalisation could provide novel molecular targets for the treatment and/or prevention of cancer.Peer reviewe