This dissertation focuses on quantifying protein folding stability determinants and presenting initial experiments that can guide the development of a novel assay that identifies cell-penetrating miniproteins. First, despite over a century of scholarship on protein folding stability, applying this knowledge to design proteins computationally remains limited. Usually, protein designers generate...
This dissertation focuses on quantifying protein folding stability determinants and presenting initial experiments that can guide the development of a novel assay that identifies cell-penetrating miniproteins. First, despite over a century of scholarship on protein folding stability, applying this knowledge to design proteins computationally remains limited. Usually, protein designers generate...
Nuclear receptors (NRs) are an important family of transcription factors that often regulate genes in response to ligands and by way of direct interactions with coactivator proteins. Many NR-coactivator pairs have been identified that cooperate to regulate transcription but fully understanding how NRs recruit specific coactivators involves learning which of...
Pattern formation of biological structures involves the arrangement of different types of cells in an ordered spatial configuration. Patterning is thought to involve the spatial organization of molecular pre-patterns that precede and drive subsequent cell differentiation and coinciding morphogenesis. These molecular prepatterns are often, although not exclusively, organized through Turing...
Eukaryotic genomes are organized into chromatin, which acts to regulate access to the organism’s genetic material. A large and diverse class of proteins, known as chromatin modifiers and remodelers, are responsible for regulating the composition and structure of chromatin by monitoring nucleosomes. Chromatin remodelers are involved in multiple cellular processes,...
The last decade has witnessed a rapid transformation in our understanding of the structure of chromatin, the nuclear complex of DNA and its structural proteins. While, barring mutations, the DNA sequence in each cell of the human body is the same, it is the structure of the chromatin complex that...
Pathogenic bacteria scavenge essential nutrients including metals, amino acids and peptides to survive within the hostile host environment. Bacteria utilize ATP-binding cassette (ABC) transporters, powered by the energy of ATP hydrolysis, to move substrates across cellular membranes. The substrate-binding protein (SBP) shuttles substrate in the periplasm and directs the substrate...
Store-operated Ca2+ entry through Orai1 channels mediate transcriptional, proliferative, and effector cell programs in many cells and are activated through a unique inside-out mechanism involving binding of the endoplasmic reticulum Ca2+ sensor, STIM1, to cytoplasmic sites on Orai1. Mutations in Orai1 that block channel activation or evoke constitutive channel activity...