Intrahepatic islet transplantation is a promising therapeutic option for the treatment of Type-1 diabetes that offers the ability to restore endogenous insulin production. Widespread use of islet transplantation is currently limited by poor survival of transplanted islets due to the harsh environment of the liver portal vein, prompting investigation into...
Nucleosome organization influences gene activity by controlling DNA accessibility to transcription machinery. In this thesis, we have developed a chemical biology approach to determine mammalian nucleosome positions genome-wide. Using this strategy, we uncover surprising new features of nucleosome organization in mouse embryonic stem cells. In contrast to the prevailing model,...
In eukaryotic organisms, genomic DNA is organized and condensed into repeating arrays of nucleosomes. The histone protein octamer of each nucleosome wraps 147 base pairs of DNA, effectively restricting access by transcription factors and other regulatory proteins to that region. An additional histone, histone H1, binds the DNA outside the...
Metabolite biosensors are powerful tools for basic biological research, medical diagnostics, and biotechnological applications. However, a generalizable strategy for developing new metabolite biosensors when an existing sensor cannot be found in nature, is a persistent challenge. Furthermore, while transcription factor biosensors have the broadest range of applications, the pool of...
Topoisomerases are ubiquitous enzymes involved in maintaining the supercoiled state of DNA in the cell. Structural, biophysical, and biochemical studies have provided an overall view of the mechanisms of DNA transformation by these enzymes, but many aspects, particularly their dynamic characteristics, remain poorly understood. Type IA topoisomerases change the topology...
Bacterial gene expression requires numerous steps that are energetically costly and tightly regulated. Following transcription of messenger-RNA, the translation of mRNA into protein is further regulated by a variety of sequence features both within and upstream of coding sequences. Collectively, these features contribute to the control of translation initiation, elongation,...
Natural products provide a renewable resource of novel chemical structures with relevance to the pharmaceutical, agricultural and materials industries. Genome sequencing has revealed that these industries currently rely on only a fraction of the number of natural products that exist in nature. Based on the impact that known natural products...
The development of metal-based probes has provided major benefits to understanding basic biological process and clinical outcomes. Metals offer access to geometries that carbon alone cannot attain, along with valuable magnetic, optical, and binding properties. Metals have proven to be particularly useful in advancing molecular imaging, a field that seeks...
Glioblastoma multiforme (GBM) is the most prevalent primary central nervous system malignancy. Due to the aggressive nature of these tumors and our inability to adequately treat them, only 3-5% of patients survive longer than 3 years post-diagnosis. The standard of care for newly diagnosed GBM is surgical resection followed by...
Regeneration is a complex biological phenomenon. Organisms that regenerate must possess robust mechanisms that direct new tissue production of the appropriate size and pattern to allow for correct and functional integration with preexisting tissue structures. Planarians are flatworms capable of regenerating from nearly any injury, making them a powerful system...