Comparative genomics

Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene.. Li, J. B. et al. Cell 117, 541–552 (2004)

Cilia and flagella are microtubule-based organelles that have been implicated in many developmental and disease processes. To identify conserved genes involved in eukaryotic cilia/flagella structure, the authors compared the proteome of Chlamydomonas reinhardtii and human to that of the non-flagellated Arabidopsis thaliana. One of the 688 conserved genes that they thoroughly characterized was a new gene for Bardet–Bieldl syndrome.

Computational biology

Programmable cells: interfacing natural and engineered gene networks.. Kobayashi, H. & Kærn, M. et al. Proc. Natl Acad. Sci. USA 101, 8414–8419 (2004)

Although engineering cells to carry out specific tasks is useful, exploiting natural circuits offers greater potential and flexibility. These authors have generated a modular genetic circuit in which a genetic toggle switch — an artificial module that can alternate between two stable states — is combined with two natural circuits: the SOS signalling pathway, which responds to DNA damage, and a transgenic quorum-sensing pathway. Four Escherichia coli strains were created, one of which forms a biofilm in response to DNA damage.

Gene therapy

LARGE can functionally bypass α-dystroglycan glycosylation defects in distinct congenital muscular dystrophies.. Barresi, R. et al. Nature Med. 6 June 2004 (doi:10.1038/nm1059)

Mutations in glycosyltransferases can cause muscular dystropies. Kevin Campbell and colleagues show that overexpressing one of these glycosyltransferases, LARGE, alleviates the symptoms of a dystrophic mouse model. Similarly, gene transfer of LARGE into the cells of humans with congenital muscular dystrophy restored glycosylation of the α-dystroglycan receptor. These results indicate that LARGE gene therapy could be an effective treatment for these disorders.

Gene regulation

Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene.. Martens, J. A. et al. Nature 429, 571–574 (2004)

Widespread intergenic transcription has been found in humans and yeast. Joseph Martens and colleagues show that when yeast is grown in rich medium, one such transcript, SRG1, is highly transcribed. Their data indicate that SRG1, which is transcribed from the regulatory region of SER3, is required to repress this gene. It seems that the reading of this transcript interferes with activator binding. So, uniquely, it is this, rather than the transcript itself, that represses SER3.