Mathew T. Holden 

Mathew T. Holden

Degree Program: Chemistry
Faculty Supervisor: Lloyd M. Smith
Phone: (608) 262-2021
Email: mtholden@wisc.edu

Current Research

There are two broad directions of research in which I'm involved. The first is aimed at developing better technologies for determining miRNA and mRNA target specificity. The second is directed towards the development and applications of nucleotide arrays, including the newly fabricated RNA version.

miRNAs are widely recognized as playing an important role in cellular biology. Despite this knowledge, accounts of miRNA function that are simultaneously complete and precise remain elusive, particularly with regard to the identification of the targets of a given mRNA. Modern computational prediction zeroes in on what is known as the “seed region” which is a short subset of the miRNA sequence known to be a dominant factor in target selection. Unfortunately, the relatively low information content of the seed region means that complementary sequences occur ubiquitously throughout large genomes and can result in an overestimation of transcripts regulated by miRNAs. Some recent evidence has also shown that a portion of interactions may occur even without perfect seed sequence complementarity, casting further doubt on our ability to predict these a priori. These difficulties have persisted in even the most current of in vivo studies, which also suffer from false positive hits. It's thought that it's possible to adapt existing methodologies in order to pair all miRNAs to their targets simultaneously and with significantly greater accuracy. Doing so is expected not only to reveal new interactions, but also to be a useful platform for monitoring cellular responses to various conditions.

Another significant area of work involves nucleotide arrays. The recent fabrication of the RNA array provides a way to parallel earlier DNA studies all while also taking advantage of the functional diversity RNA offers. While DNA arrays are not a new technology, a number of resources available to the group allow enzymatic reactions to be carried out at the surface. This enables the study of a number of processes in which I have an interest including the sequence determinants of polymerase function and the extension of the group's earlier work in gene synthesis.

Abstract (PDF)

Resume (PDF)

 

 

 


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