On Thursday Helen Blackwell from the University of Wisconsin Madison braved the cornfields and soybeans that pave the way south to the U of I and gave an awesome seminar. Unfortunately I didn't get to go out to lunch with her, but several other members of my group did. From what I hear, she is quiet, witty, observant, and very interested in hearing what students have to say. Although I was a little disappointed that she didn't mention much about her group's work on small molecule macroarrays, she did discuss their recent article on quorum sensing in Vibrio fischeri, which is a fascinating story for anybody interested in chemical biology. She even satisfied those hard-core organic chemists with some microwave assisted reactions. If I remember correctly, they have been able to reduce the reaction time from 24-48 hours to under 30 minutes for the final cyanogen bromide mediated cyclization step in the synthesis of N-phenylacetanoyl-L-homoserine lactones. Pretty amazing what microwaves can do.Bacteria are able to control their population growth through a process called quorum sensing. By releasing certain molecules into their media, bacteria can signal to each other and thus are able to alter their mode of growth; essentially this communication allows them to function as muticellular communities rather than single celled organisms. Gram negative bacteria are known to use N-acylated-L-homoserine lactones (AHLs) for communication. Previous studies have shown that phenylacetanoyl-L-homoserine lactones (PHLs) can act as antagonists of quorum sensing, so Blackwell and coworkers created a small library of PHLs and tested their activity in the bioluminescent bacteria Vibrio fischeri. While this library contained less than 30 compounds, it included some of the best antagonists AND agonists of gram-negative bacteria that are known to date. Very small structural changes elicited huge differences in activity.
In my opinion, one of the most interesting points of the talk was Blackwell's discussion of the Hawaiian bobtail squid. Apparently its light organ (which is used for hunting and prevents the squid's shadow from alerting potential predators/prey to its position) is inoculated with V. fischeri shortly after birth. Quite an interesting symbiotic relationship--the squid provide the bacteria with a home and food source in exchange for light. Blackwell shared some preliminary data with us indicating that the superagonist discovered in the small PHL library is well tolerated and active in vivo. The juvenile squid utilized for these experiments are tiny enough to fit into the wells of a 96-well plate, and in my opinion they are very cute (as illustrated by the picture above, V. fischeri image from Geske, G.D. ; O’Neill, J.C.; Blackwell, H.E. (2007) ACS Chemical Biology 2(5), 315-320.).
In my opinion, one of the most interesting points of the talk was Blackwell's discussion of the Hawaiian bobtail squid. Apparently its light organ (which is used for hunting and prevents the squid's shadow from alerting potential predators/prey to its position) is inoculated with V. fischeri shortly after birth. Quite an interesting symbiotic relationship--the squid provide the bacteria with a home and food source in exchange for light. Blackwell shared some preliminary data with us indicating that the superagonist discovered in the small PHL library is well tolerated and active in vivo. The juvenile squid utilized for these experiments are tiny enough to fit into the wells of a 96-well plate, and in my opinion they are very cute (as illustrated by the picture above, V. fischeri image from Geske, G.D. ; O’Neill, J.C.; Blackwell, H.E. (2007) ACS Chemical Biology 2(5), 315-320.).
