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Genome stitched together by hand

Scientists have succeeded in stitching together an entire bacterial genome, creating in the lab the full set of instructions needed to make a living thing. The stage is now set for the creation of the first artificial organism — and it could be achieved within the year.

The genome for the pathogenic bacterium Mycoplasma genitalium was made in the laboratory by Hamilton Smith and his colleagues at the J. Craig Venter Institute in Rockville, Maryland. The genome has 582,970 of the fundamental building blocks of DNA, called nucleotide bases, making it more than a factor of ten longer than the previous-longest stretch of genetic material created by chemical means.

Now the team at the Venter institute, which includes the institute’s founder, genomics pioneer Craig Venter, will aim to discover whether cells can be ‘booted up’ into action when loaded with this genetic programme. “This is the next step and we are working on it,” says Smith.

Venter and his colleagues have already managed to transplant the DNA from one bacteria into another, making it change species (see Genome transplant makes species switch/news070625-9). These bacteria were closely related to M. genitalium. If the transplant can be repeated with a man-made genome adapted from M. genitalium, the result could qualify as the first artificial life form (see 'What is artificial life?').

http://www.nature.com/news/2008/080124/full/news.2008.522.html

The DNA damage response pathways: at the crossroad of protein modifications

To ensure faithful duplication and inheritance of genetic material, the cell has evolved with the ability to detect and propagate the initial DNA damage signal to elicit cellular responses that include cell cycle arrest, DNA repair, senescence and apoptosis, which collectively have been termed the DNA damage response. Dysregulation of components involved in these processes contributes to genomic instability, which in turn leads to tumorigenesis. This is supported by the fact that clinical mutations in proteins that play a role in the DNA damage response often predispose individuals to cancer development 1. The link between genomic instability and tumorigenesis is perhaps most exemplified by the human genetic disorder ataxia-telangiectasia (A-T). A-T is caused by mutations of the ATM gene, the product of which is intimately involved in the DNA damage signaling network. A-T patients are characterized by neurodegeneration, radiosensitivity, immunodeficiency and cancer predisposition 2, 3. Recent studies indicate that the ATM protein kinase modulates multiple branches of signaling pathways by phosphorylating and regulating its substrates in response to DNA damage, failure of which contributes to genomic instability and tumorigenesis 4. Like ATM, mutations in NBS1 have also been documented to predispose individuals to the genomic instability disorder Nijmegen breakage syndrome (NBS) 5. Patients with hypomorphic mutations in NBS1 manifest microcephaly, immunodeficiency, radiation sensitivity and are prone to carcinogenesis. The close resemblance between NBS and A-T patients suggested a functional relationship between these gene products. Indeed, the MRN complex consisting of Mre11, Rad50 and NBS1 not only has been implicated as one of the initial DNA lesion sensors, but also is believed to be required for efficient ATM activation following DNA damage. As such, the understanding of molecular pathways that function to safeguard the integrity of the genetic material is critical for early detection and offers potential treatments for cancer patients.

http://www.nature.com/cr/journal/v18/n1/full/cr2007109a.html

Biopolis is a purpose-built biomedical research hub

Conceived as the cornerstone of a much broader vision to build up the biomedical sciences industry in Singapore, the Biopolis is a purpose-built biomedical research hub where researchers from the public and private sectors are co-located. Situated in the south-western part of Singapore, the Biopolis is within walking distance of the Buona Vista MRT Station and is near both the National University of Singapore and the National University Hospital.

Phase 1 of Biopolis comprises of a seven-building complex linked by skybridges and offers a built-up area of 185,000 sqm. Two buildings, Chromos and Helios, are dedicated to biomedical players from the private sector. The other five buildings (Centros, Genome, Matrix, Nanos and Proteos) house five of the seven biomedical research institutes under the Agency of Science, Technology and Research (A*STAR), Singapore's lead agency for scientific research and development under the aegis of the Ministry of Trade and Industry. These five research institutes are the BioInformatics Institute (BII), the Bioprocessing Technology Institute (BTI), the Genome Institute of Singapore (GIS), the Institute of Bioengineering & Nanotechnology (IBN) and the Institute of Molecular and Cell Biology (IMCB).

http://www.a-star.edu.sg/astar/biopolis/index.do