2004 - 2005 Winners
Tom McCarthy and Trenton Pruden

Tom McCarthy's Research Proposal (November, 2004):
Research director: Dr. Juliane Soukup

    The research that I have been involved in and propose for this scholarship deals with control of gene expression through RNA structural changes, without the need for proteins.  These novel RNA structures (riboswitches) can bind small cellular metabolites and turn gene expression on or off.  My research involves one of these novel riboswitches, specifically one whose activity is dependent upon the metabolite glucosamine-6-phosphate.  This riboswitch exerts genetic control through self-cleavage in the 5’-untranslated region of the messenger RNA (mRNA).  This cleavage, which is enhanced over a thousand fold in the presence of glucosamine-6-phosphate, down-regulates gene expression.  While it has been observed that this particular riboswitch’s activity is substantially increased in the presence of glucosamine-6-phospate, the interaction that occurs between metabolite and riboswitch is not well understood.  It is toward the better understanding of this interaction that my research focuses.
    The first step that was undertaken in the study of the RNA-metabolite interaction was to try to determine the important functional groups on the metabolite that interact with the riboswitch.  In order to accomplish this, analogs of the true metabolite were studied.  These molecules varied from those with very similar structures to glucosamine-6-phosphate, such as glucose-6-phosphate, all the way down to something as simple as methyl-amine.  A successful analog was a molecule that when allowed to interact with the riboswitch promoted self-cleavage at a greater rate than when no analog was present.  The result of this portion of my research was that the most important functional group on any analog molecules was the amine group.  In addition, results showed that the closer the structure of the analog to the true metabolite (provided it contained the amine group), the greater the rate of self cleavage.  The most efficient analog promoted cleavage three hundred fold over background.  Given the fact that an amine proved essential in the promotion of self-cleavage, it is predicted that it is involved in the catalytic mechanism of the reaction.


Tom McCarthy's Research Report (May 2005)


Trenton Pruden's Research Proposal (November, 2004):
Research director: Dr. Mark Freitag

     The gas-phase reaction of chlorine nitrate with un-ionized HCl produces photochemically liable chlorine gas.  Photolysis of Cl2 produces chlorine radicals capable of destroying ozone.  Hillier  concluded that the reaction of ClONO2 and HCl will occur readily at stratospherically relevant temperatures when in the presence of just 2 water molecules.  Our research continues Hillier’s exploration of the activation mechanism of ClONO2 by HCl with water as a catalyst using electronic structure methods.  Our initial task was to reproduce the data obtained by Hillier using GAMESS—General Atomic and Molecular Electronic Structure System.  This Unix-based computer program can calculate a wide range of quantum chemical properties.  Our first goal is to recreate the reaction mechanism between ClONO2 and HCl by using GAMESS to process Hillier’s data.  We will compare our data to the values Hillier calculated in order to find and eliminate any significant differences.  Once the proper background work has been completed, we will introduce water molecules into our computer-generated scenario and observe what effects water has on the reaction path and relative energies.  Finally, we will introduce into GAMESS a model of solid ice with hundreds of fixed water molecules using the Effective Fragment Potential method  (EFP) in order to discover how ice would theoretically affect and catalyze the reaction mechanism between ClONO2 and HCl.

1. Hillier, I. H.; Tresadern, G.; McNamara, J. P.  J. Phys. Chem. A 2000, 104, 4030-4044.
2. Gordon, M.; Freitag, M.; Bandyopadhyay, P.; et al.  J. Phys. Chem. A 2001, 105, No. 2, 293-295

Trenton Pruden's Research Report (May 2005)