published_or_final_version / Biochemistry / Master / Master of Philosophy

No description available.

No description available.

No description available.

No description available.

Quantitative analysis of Drosophila melanogaster gap gene expression data reveals valuable information about the nature and strengths of interactions in the gap gene network. We first explore different models for fitting the spatiotemporal gene expression data of Drosophila gap gene system and validate our results by computational analysis and comparison with the existing literature. A fundamental problem in systems biology is to associate these results with the inherent cause of gene regulation, namely the binding of the transcription factors (TF) to their respective binding sites. In order to relate these expression-based estimates of gap gene regulation with the sequence-based information of TF binding site composition, we also explore two related problems of (i) finding a set of regulatory weights that is proportional to the binding site occupancy matrix of the transcription factors in current literature and (ii) finding a set of position weight matrices of the TFs that produce a new binding site occupancy matrix showing a greater level of proportionality with our regulatory weights. Our solution to the first problem yielded a regulatory weight matrix incapable of explaining the true causes of gene expression profile despite its relative numerical accuracy in predicting the gene expressions. On the other hand, the second optimization problem could be solved up to a reasonable level of accuracy, but further analysis on the result demonstrated that this optimization problem may be under-constrained. We devise a simple regularization strategy that helps us to reduce the under-constrained nature of the problem.

Attaining an understanding of the mechanisms underpinning development has been amongst the cardinal scientific challenges of our age. The transition from a single cell organism to the level of complexity evidenced in higher eukaryotes has been facilitated by the advent of intricate developmental networks involving a plethora of factors that synergise to allow for precise spatio-temporal expression of the proteins present in higher organisms. Development is often portrayed as a domino like cascade of events stemming from relatively uncomplicated origins that go on to branch out and form associations and interactions amongst multitudinous actors that will inexorably lead towards a higher state of order. Transcription factors occupy a central position within this tapestry of interactions. They regulate expression of the various required proteins and they provide the cues for the developmental events that will eventually shape an organism. These factors frequently remain unknown until some occurrence causes developmental processes to fail and inadvertently focus attention on the factors that facilitate development. Myotonic dystrophy is a useful paradigm of such a developmental dysfunction that has led to the discovery of a transcription factor integral to both muscle development and gonadogenesis in both Drosophila and higher eukaryotes.

No description available.

Tal-1 is a transcription factor that is frequently ectopically expressed in the majority of cases of T-cell acute lymphoblastic leukemia (T-ALL). The ectopic expression of Tal-1 in patients with ALL has been found to decrease susceptibility to chemotherapeutic drugs and apoptosis. Thus, this study focuses on the effects of endogenously expressed Tal-1 in the Jurkat cell line on three Bcl-2 family members (Bcl-2, Bcl-xL, and Bid) and the inhibition of apoptosis and cell viability when exposed to apoptosis inducing drugs such as etoposide. The data obtained indicate that when treated with etoposide for 12 h Jurkat cells endogenously expressing Tal-1 have an 81% higher level of anti-apoptotic Bcl-2 expression, an 18% lower level of anti-apoptotic Bcl-xL, expression, and a 31% lower level of pro-apoptotic Bid expression compared to Jurkat cells lacking Tal-1 expression. The data also demonstrates that Jurkat cells endogenously expressing Tal-1 have a 15.94% lower amount of cell death after treatment with etoposide for 12 h and a 20.34% lower amount of cell death after treatment with etoposide for 24 h when compared to Jurkat cells that lack Tal-1 expression. Thus, the endogenous expression of Tal-1 increases the amount of the anti-apoptotic Bcl-2 expression and decreases the amount of the pro-apoptotic Bid creating an overall anti-apoptotic signal within the cell. / Department of Biology

Mouse models (that develop or can be stimulated to develop lymphomas) are used to examine cancer-related processes. Mouse models can be effective tools used to identify new, early, and pre-malignant markers of lymphomas. Signal Transducer and Activator of Transcription (STAT) 6 is a transcription factor activated through the Jak-Stat pathway. Transgenic mice expressing a constantly activated Stat6 (Stat6VT) were previously generated and characterized to have altered lymphocyte homeostasis. Some of these Stat6VT mice developed a lymphoproliferative disorder (LPD). LPD, including lymphomas, develops when lymphocytes are overproduced or act abnormally. These Stat6VT mice may serve as a model for examining lymphoma development. In order to characterize the altered lymphocytes and determine if LPD observed in the Stat6VT mice is characteristic of lymphoma, RT-PCR analysis and Western analysis were done to examine if the presence of Stat6VT alters the expression of the cell cycle genes Gfi-1 and Gfi-1b and if these genes differ in LPD Stat6VT verses control mice. / Department of Biology