Dear Dr. Mc Fadden (Geoff)
My wife (Elizabeth Pilon-Smits) and I (Marinus Pilon) are faculty members in the Biology department at Colorado State University. We are looking for places to do Sabbatical research and we thought your lab would be a really good place.
My own research focuses on cofactor assembly in chloroplasts (Cu and Fe cofactors). My wife, Elizabeth Pilon-Smits is interested in various aspects of plant Se and S metabolism. Together we have a joint project on Iron-sulfur cluster assembly in plastids (please view our web site at: http://rydberg.biology.colostate.edu/epsmitslab/; if you are interested we can also forward more updated CVs). Plants have a unique Fe-S assembly system, and I think the same or a similar system may be present in the Malaria parasite. However I think nobody showed it so far.
I have been interested in the apicoplast of apicomplexans for some time. The question is what is its function? I have a hypothesis. Green chloroplasts carry out biochemistry that produces and is tolerant to oxygen and reactive oxygen species. An oxidative burst is a common host defense mechanism against parasites. What if the apicoplast provides the defense against such oxidative attack by utilizing its oxygen tolerance capacity in metabolism? A simple idea but I think it makes sense. The plant Fe-S assembly machinery is most similar to the bacterial systems that operate under oxidative stress and Fe-S clusters are so essential to many aspects of metabolism.
I have requested and received an mRNA sample from Carolina Barrilas' lab at NIH and we are trying to clone (so far just one PCR) the cDNAs for the plasmodium apicoplast NifS and SufE homologs. Right now this is still a side project. As a first step I just want to see their enzymatic activity (after heterologous expression in E. coli) and their regulation in vitro. If we succeed in getting the proteins expressed we can raise antibodies. Our lab has a lot of expertise in the assembly of metal ion cofactors in plants and we are good at plant genetics and cell biology and at biochemistry. However, we know nothing of culturing or working with apicomplexans. That type of research I would like to approach collaboratively.
Things I would like to do in a sabbatical in your lab:
- localize the Fe-S assembly proteins
- characterize expression/regulation
- if possible, study a KO or RNAi knock down
- look for downstream targets: Fe-S proteins in the apicoplast
- I would also think about looking at Cu delivery proteins
Elizabeth and I could work on this together but she may also have an interest in possible other trace elements such as Se.
I bet that the apicoplast FeS assembly system will indeed be different from the mammalian system, and if so, people can use this info to design potential inhibitors/drugs that target the unique properties of the parasitic Fe-S assembly system but leave the host machinery untouched. Since iron-sulfur clusters are essential for much of the central metabolism of any cell, this approach has good promise for treatment of malaria and toxoplasmosis (yes I have a tendency to get carried away). In the short term, I am just really interested in learning about the function of the malaria/toxoplasma plastids and the similarities with green plants.
A little more about us: We both got our PhD at Utrecht University, The Netherlands. Elizabeth did her Ph.D working on the evolution of Crassulacean Acid Metabolism in plants, followed by a postdoc using plant biotechnology to enhance drought resistance. She then did a post doc in Berkeley, working in Norman Terry’s lab on selenium and metal phytoremediation. Her present research is on various aspects of trace element metabolism in plants, with a focus on Se and S and possible applications in phytoremediation. More recently she is working on a nice project on the evolutionary and ecological significance of plant Se hyper-accumulation. I am as much a biochemist as a biologist. For my Ph.D and first post-doc, I studied protein import into chloroplasts. I then did a post-doc in Berkeley studying protein secretion in yeast in Randy Schekman’s lab. Right now I use Arabidopsis to study plastid cofactor assembly.
I am not sure, but hope our combined expertise could be beneficial to your lab during a sabbatical, and that we can set up a lasting collaboration.
We are still looking for funding. The university pays half of our salary, and we plan to request a Guggenheim fellowship. We are from Holland, permanent residents in the US but we do not qualify for Fulbright. If you are interested in having us visit your lab, we would like to also explore whether the University of Melbourne has any short-term fellowship opportunities for visiting professors. We would also be able to contribute to teaching if desired. The time period we have in mind would be the first few months of 2008.
Sorry to make it so long.
We look forward to hearing what you think!
With very best wishes
Marinus (and Elizabeth).
PS: In case it is beneficial to have more than one host (e.g. for Uni Melbourne's interest): two other faculty at your university whom we'd also like the opportunity to interact with are Chris Cobbett (Genetics) and Alan Baker (Botany). We haven't contacted them yet.