DNA-binding domain

to itself forming homodimers or heterodimers. Dimerization of STAT proteins allows the homodimer/heterodimer to be translocated to the nucleus where it then binds to gamma activated sequence (GAS) elements within the nucleus. Binding of STAT proteins to GAS elements in the DNA leads to the transcription of target genes which ultimately play a crucial role in cellular viability, survival, apoptosis, etc. (1,2) Activation of the JAK/STAT pathway is responsible for initiation of multiple signal transduction

important to note that glucocorticoid’s bioavailability is between 60% and 100%. More than 90% of the circulating glucocorticoid binds to corticosteroid binding globulin (CBG). Furthermore, the hormone in the circulation that is free and unbound, then binds to the glucocorticoid receptor (GR). GR consists of a carboxy terminal ligand binding domain, a

that were designed for sequence-specific binding of the DNA. One of the first breakthrough methods of gene targeting was the usage of chimeric proteins called zinc-fingers nucleases (ZFN) to create double-strand breaks. Still, the real revolution was the introduction of CRISPR and CRISPR associated (Cas) systems into the biomedical research arena. One specific CRISPR nuclease – Cas9 – paired with short guide RNA has the ability to recognize the target DNA via Watson-Crick pairing. The guide sequence

Chapter 1: Introduction 1.1 RNA interference regulates gene expression in eukaryotes The flow of genetic information within a living organism was first stated by Crick as “DNA makes RNA and RNA makes protein” (Crick 1956). In response to environmental stimuli, the dynamic modulation of specific gene products (mRNAs and proteins) confers flexibility and adaptability to prokaryotes, eukaryotes, and viruses (Crick 1956). Proper gene regulation is essential for cell growth, development, proliferation

of a protein can be regulated by different mechanisms including degradation (7, 8), molecular crowding (9), disulfide bond formation, and small molecule binding (10-12). In addition to controlling the absolute level of a protein, the activity of a protein can also be regulated by covalent modification, interaction with other proteins, or binding of small molecules. Covalent modification of a protein involves the attachment of a functional group resulting in phosphorylation (13, 14), glycosylation

invasive genetic material. Methods Three types of CRISPR mechanisms, the most studied type II, have been described. In Type II, DNA is infected from viruses or plasmids, subdivided into small pieces, and incorporated into a CRISPR locus between a series of short repeats (about 20 bps). The loci are transcribed

acids and is considered a phosphoprotein. The gene also contains four domains, also called units. Each one of these domains has a different responsibility. One domain, called the core domain, identifies specific DNA sequences. Another domain stimulates transcription factors. The third domain controls the tetramerization of the protein. The last domain is able to distinguish damaged DNA. This may include single-stranded DNA or base pairs that are misaligned (Vijayaraj). The gene also contains

(i) attachment of the viral gp120 to the CD4 T cell receptor, (ii) binding of the gp120 to CCR5 or CXCR4 co-receptors and (iii) fusion of the viral and cellular membranes HIV entry into the cell is mediated by its trimeric envelope (Env) glycoprotein gp120/gp41 complex and it happens in two major steps. [1, 2, 4] First, the surface subunit gp120 binds to the cell receptor (CD4) and a co receptor (CCR5 or CXCR4). Upon receptor binding, the gp41 which is originally sheltered by gp 120, undergoes a dramatic

stems from the observation that genotypically identical cells can exhibit alternative and stably heritable phenotypes. These traits, along with the chromosomal mechanisms that produce them and ensure their propagation without alterations in the primary DNA sequence, are referred to as “epigenetic.”(7-9). Alternatively, regions in the genome where the epigenetic state varies and results in alternative phenotypes are referred to as “epialleles” (10). Epigenetic variation adds a regulatory layer to genome

Since the invention of saccharin in 1879, artificial sweeteners have taken the world by storm. From being used in both World War I and II as a cheaper, more accessible replacement for the rarer and dearer table sugar - to more recently being associated with weight loss and a sugar-substitute for diabetics. Arguably, our excessive consumption of natural sugars is a huge factor in the so called obesity epidemic, which has opened up the market for sweeteners. Non-nutritive artificial sweeteners such