The Buchmueller research group is investigating how proteins interact with DNA. We are particularly interested in the HMGA family of proteins, which are linked to cancer metastasis. These proteins are intrinsically disordered and have been difficult to characterize, but there are a variety of biophysical techniques that have provided insight into the molecular nature of how these proteins interact with DNA. It has been long known that HMGA proteins bind the minor groove of AT rich DNA using AT hook motifs. Much of our research utilizes peptides that mimic AT hook motifs, so we can use biophysical techniques to understand the interactions between these AT hooks and DNA. Specifically, we have used isothermal titration microcalorimetry (ITC) to characterize the effects of salt, temperature and DNA sequence on AT hook interactions with DNA.
For a variety of reasons, including the disordered structure of these proteins, it is difficult to develop therapeutic targets against HMGA proteins. We seek to better characterize the interactions with DNA so that a therapeutic model can be developed. For example, we are looking at the competition between small molecules and the peptide mimics at the molecular level to gain insight.
Students in the Buchmueller lab will use a variety of biophysical, bioanalytical and molecular biology techniques to understand how small molecules and/or proteins interact with DNA.