A disconnect exists between the behavior of transcriptional and genetic regulation in bacterial systems when comparing phenotypic patterns and dynamics of a population to those observed at the single cell level. In this thesis, we developed a number of tools and assays to better understand, overcome, and predict the challenges...
The ability to track labeled cancer cells in vivo would allow researchers to study their distribution, growth and metastatic potential within the intact organism. Magnetic Resonance (MR) imaging is invaluable for tracking cancer cells in vivo as it benefits from high spatial resolution and absence of ionizing radiation. However, many...
The circadian clock is a biological oscillator present in all terrestrial life forms that aligns organismal functions with the daily rising and setting of the sun. In mammals clocks are expressed both in pacemaker cells in the brain that are directly entrained by light as well as in all peripheral...
Fungi have an immense untapped store of natural products, small molecules that can often be repurposed as pharmaceuticals. The genes that encode secondary metabolic machinery are often genomically co-localized into biosynthetic gene clusters. Because of the immense energetic costs that goes into producing the biosynthetic pathway and its products, strict...
In yeast, inducible genes such as INO1, PRM1 and HIS4 reposition from the nucleoplasm to nuclear periphery upon activation. This leads to a physical interaction with nuclear pore complex (NPC), interchromosomal clustering, and stronger transcription. Repositioning to the nuclear periphery is controlled by cis-acting transcription factor (TF) binding sites located...
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...
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...
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,...
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...
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...