Friday, May 09, 2008

Letting go - now back to Leishmania

Letting go is hard to do, especially when you have fought tooth and nail to get your point across and went through some crazy times. I recently attended the "God Be in My Head" event at the Dana Centre, where a panel chaired by Colin Blakemore discussed the possibility of so-called "God spots" in the brain, and although epilepsy and schizzophrenia were mentioned as possible links to abstract thinking, creativity and spiritual experience, I was surprised to observe that no-one at the event mentioned mania, which seems to me to lie at the intersection between the two other states of mind. One of the best suggestions of the evening was the idea to analyse the brain activity of problem-solving scientists using functional MRI and to try to compare the results to the brain scans of nuns praying or monks meditating. I like it even though I am getting a bit tired of functional MRI papers, but somehow I don't see that experiment being carried out any time soon, the eureka experience and phenomena such as calculation-induced halucinations are science's dirty little secrets and I doubt whether scientists really are prepared to address these issues.

At any rate, I'm digressing, whilst it is fun to rejoin the scientific debate and to watch my representation of the genetic code climb the "google charts", I have to let go of certain ideas and redirect my focus on my PhD. Consequently, I find myself thinking more and more about Leishmania these days. Given that S-adenosyl methionine (SAM) is involved in a number of different cellular processes possibly affecting the replication of intracellular parasites, how would it be possible to differentiate the effects of the individual processes? The ones I am particularly interested in are polyamine synthesis and DNA methylation. Would it be enough to add radiolabelled SAM to infected cells and to try to see where the marked methyl group might end up? Is there radiolabelled SAM available in which the non-methyl carbon atoms are 14C, making the substance useful in tracking polyamines? Whilst I would try to focus on in vitro experiments at first keeping things as simple as possible, I also wonder what in vivo experiments might look like. What effect might adding or depleting SAM have in vivo? What about methylthioadenosine (MTA), a product of the SAM catabolism that arises after the polyamine synthesis step? How could the effect of SAM derivatives be untangled from possible changes to cytokine production?

Too many questions for me to answer...

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