When I’m not too busy raging at skuptaloids online, I enjoy molecular biology and mycology, the study of fungi. Towards those ends, I’m visiting the Duke Symposium in Celebration of Mycology and Mycologists. I was only able to attend a few afternoon lectures on the first day of this conference, but am enjoying it greatly! Some of the lectures I attended:
“Glycoengineered yeast: from platform to product”
Discussed the engineering considerations is convincing yeasts to produce biochemicals – for example, drugs. A major challenge is in glycosylation, the addition of complex sugars to proteins. Glycochemistry is very interesting to me; it is still very much a biochemical frontier.
“Membrane lipids and fungal virulence”
Glucosylceramides in fungi and humans are different, with fungal compounds featuring an unsaturated site and a methyl side group. Humans and fungi also have slightly different enzyme active sites to deal with these differences, suggesting that drugs can be developed to target the active sites in fungal pathogens without disrupting human biochemistry. The drug candidates discussed actually have analogs in commercial fungicides.
“Inositol sensing and Cryptococcus virulence”
Inositol, an alcohol carbohydrate, is available as a carbon source for Cryptococcus fungi, and its abundance in animal brains explains their attractiveness as a habitat – unfortunately, this causes meningitis in the host.
“From function to form: moving toward structural analysis in Cryptococcus neoformans”
A discussion with focus on Ras proteins, chemical switches strongly conserved amongst eukaryotes, and which are involved in fungal thermotolerance – that is, their resistance to temperatures like that of the human body. There was also a discussion of farnesylation, a post-transciption protein modification scheme in which an organic farnesol group is added to the end of a protein chain; in fungi, this modification is important in making sure the relevant proteins embed in cellular membranes where they do their job; interrupting this step causes the proteins to float uselessly in the cell matrix. Interestingly, farnesyltransferase inhibitors have already shown promise in a number of other fields, including anticancer and antiparasite applications.
“Nutritional adaptation of Cryptococcus neoformans to the host environment”
Concentrates on the role of iron in Cryptococcal behavior – high iron conditions leads to the formation of large capsules; indeed, “Iron overload exacerbates cryptococcal meningoencephalitis” I am very interested in the biochemistry of iron; as the speaker noted, there is a competition between the host and the parasite for available iron, which is bound by enzymes like transferrin. If iron intake exceeds the body’s ability to produce the binding enzyme, you may wind up seeding parasites. (E.g. Nesse & Williams 1994, p. 29-30) I think this is especially interesting in light of the observation that ocean fertilization experiments can fertilize toxic species as well as benign ones (Trick et al. 2010). Also some interesting discussion of fungal siderophores (*swoon*) and melanins as regulating the oxidation state of environmental iron – and consequentially, its uptake.
That was it for this afternoon – hopefully I’ll wake up in time for tomorrow’s conference! (I’m not a morning person, what can I say…)
Randolph Nesse, & George Williams (1994). Why We Get Sick: The New Science of Darwinian Medicine. Vintage Books: New York
Trick, C., Bill, B., Cochlan, W., Wells, M., Trainer, V., & Pickell, L. (2010). From the Cover: Iron enrichment stimulates toxic diatom production in high-nitrate, low-chlorophyll areas Proceedings of the National Academy of Sciences, 107 (13), 5887-5892 DOI: 10.1073/pnas.0910579107
Turnbull, J., & Field, R. (2007). Emerging glycomics technologies Nature Chemical Biology, 3 (2), 74-77 DOI: 10.1038/nchembio0207-74