Sorek, et al. Nature Rev Microbiol 2008
CRISPRs are clustered, regularly interspaced short palindromic repeats found in bacterial genomes. Together, with a leader sequence and CRISPR-associated (CAS) genes, they believe that this system helps prevent phage infection....P.S. I didn't know phage were 5-10x more numerous than bacteria!
So, yea, they think this is a bacterial homolog (paralog?) of eukaryotic RNAi. They're still working out the details, but there are already patents on this for three applications, namely strain spoligotyping (spacer oligotyping), engineering phage resistance in industrial bacterial strains used to make dairy products, and engineering gene knockdown in bacteria. The cool thing is that because the spacers are numerous and repetitive, you could knockdown several genes with this machinery....but apparently, it's still not proven that it has RNAi function.
CRISPR Interference Limits Horizontal Gene Transfer in Staphylococci by Targeting DNA
Marraffini, et al. Science 2008
So, I think the title says it all, but to go on, they found a clinical strain of Staph. epidermis that has CRISPR loci with part of the nickase gene inside, a gene found in all staphylococal conjugative plasmids (recall conjugation is a form of either intra- or interspecies horizontal gene transfer).
Blah, blah, blah, complicated genetics that I don't really understand right now, and ...oh, what's this?
Apparently, they proved that CRISPR doesn't target RNA - it targets DNA! Also interesting is their concluding few lines:
"CRISPR function is not limited to phage defense, but instead encompasses a more general
role in the prevention of HGTand the maintenance of genetic identity, as with restriction-modification systems.A primary difference between restriction modification and CRISPR interference is that the latter can be programmed by a suitable effector crRNA. If CRISPR interference could be manipulated in a clinical setting, it would provide a means to impede the ever-worsening spread of antibiotic resistance genes and virulence factors in staphylococci and other bacterial pathogens."
Perhaps I'll follow up on this after a careful re-read and class discussion tomorrow morning.
Man, I just can't keep up on here with the amount of science that I take in everyday. I still haven't gotten to write entries about any of my lab work. And just yesterday, I was skimming an article (probably in Nature) about genetically modified animals and the legal implications of their potential approval. They talked about how there weren't too many companies working on it, but that they had developed the Enviropig, whose salivary glands secrete an enzyme that helps reduce the pig's phosphorus waste.
(Picture from the UCSD news website)
And in today's Chemical Biology lecture, we discussed how GFP was developed (for which the 2008 Nobel Prize was awarded in Chemistry) as well as its colored variants. While I could go into detail on how it works, I'll just mention that the coolest application I thought was the "Brainbow", where this lab at Harvard used a Cre-recombinase system to label 1000s of murine neuronal cells with varying combinations of CFP, YFP, GFP, and RFP. They claim this will help them dissect the complex network of connections between cells in the brain. Certainly looks pretty : )Disulfide Isomerization After Membrane Release of Its SAR Domain Activates P1 Lysozyme
Xu, et al. Science 2005
These authors argue about the activate-ability of lysozymes using cysteine-accessibility experiments.
No comments:
Post a Comment