Research

Oxidative Damage to RNA

RNA damage resulting from oxidative stress has been linked to the cause/result of different diseases, i.e., Alzheimer’s disease, muscle atrophy.  It is likely that oxidative lesions interfere with the functions between RNA and other cellular molecules.  Examples of oxidatively damaged nucleobases that have been found in natural systems are depicted below.


We are interested in finding if a direct correlation between oxidative damage to RNA and how it may lead to the disease exists i.e., exploring mechanisms that result in defects in protein synthesis.  Using a combination of bio-organic techniques we are in the process of developing suitable models that may shed more light on this topic.


RNA-Small Molecule Interactions

Molecular recognition using nucleic acids may be used as a way to identify potential targets that inhibit/enhance known signaling pathways in a variety of natural systems.  Examples in nature include aptamers composed of both DNA or RNA and that are specific for theophylline (a known bronchodilator), cocaine and pre-Q1.  Upon binding of the corresponding target molecule, the biopolymers fold into a distinct structure i.e., (A) hairpin, (B) double stranded, (C) pseudoknot that then goes on to perform a specific function.

Figure 2.  Examples of aptamers are depicted:  The RNA-based aptamer (A) recognizes theophylline (JACS, 2005 Mecozzi et al.) to form a hairpin, whereas the pre-Q1 class I riboswitch (C) recognizes its target and gives rise to pseudoknot formation (JACS, 2012, Resendiz et al.).  The DNA-based split aptamer (B) recognizes cocaine and brings the two strands together (JACS, 2011, Heemstra et al.)

We are interested in the design and synthesis of RNA-based structures that can be used as sensors for small molecules in order to explore their potential for applications in biologically relevant systems i.e., finding good candidates for therapeutic purposes.