As part of the interdisciplinary nature of the course, the MSc program required the completion of three mini projects, each lasting 8 weeks and taking place in one of the three disciplines of Chemistry, Biological Sciences and Mathematics/Computing.

 

Chemistry:

"Study of Cys-270 in C-C Hydrolase Enzyme MhpC"

Supervised by Prof. Timothy Bugg, with additional help from Dr. Jian-Jun Li, Chen Li and Rachel Marrington.

The C-C bonds of aromatic Carbon compounds can be extremely difficult to break. Many petro-chemical pollutants contain aromatic Carbon compounds, making them very difficult to break down in the environment. Various techniques are available, and one such method is to use micro-organisms that have developped pathways for the breakdown of benzenoid rings. In this project we examine the role of Cys-270 in the enzyme MhpC, found to be essential in the aerobic benzene cleavage pathways of E. coli. This amino acid is found close to active site of the enzyme, and is suspected to have interactions with the Histodine of the Catalytic Triad. Also, thiol modification of Cys-270 results in inactivation of the enzyme, suggesting a crucial role in the catalytic capacity of MhpC. By studying this role, it is hoped that a better understanding of the pathways may be established, leading to improved use in pollution breakdown.

For more information, please see Dr. Timothy Bugg's website.

This project was presented in a poster form at the 2004 MOAC conference, held at Poppit Sands. The poster is available for viewing here .

 

Biological Sciences:

"Changes in Gene Expression During Reversal of Myc Induced Cancer"

Supervised by Michael Khan and Stella Pelengaris with additional help from Linda Cheung, Vicky Ifandi and Sylvie Abouna.

The oncogene c-Myc is found to be deregulated in a variety of human cancers, and is often associated with aggressive, poorly differentiated tumours. The gene encodes a transcription factor involved in several biological processes, most noticeably in cell proliferation and, oddly enough, apoptosis (programmed cell death). It has been shown that a single genetic lesion, resulting in unmediated expression of c-Myc, is sufficient to result in carcinogenesis. This goes against the wildly held view that several such lesions were necessary. Deregulated expression of c-Myc in pancreatic islets results in islet involution and onset of diabetes due to the loss of insulin production. The apoptotic activity of the oncogene outweighs the prolific activity. A second lesion is introduced to the model to suppress apoptotic activity, allowing study of the onset of tumorogenesis. This model shows that two simple genetic lesions are sufficient to result in hyperplastic insulinomas among the islets. However, the most exciting result from this experiments that these lesions are not only sufficient to produce carcinomas, they are required. Subsequent deactivation of c-Myc results in complete islet involution, and a return to normal function after 38 days. This may lead to a new gene-specific therapy for the treatment of Myc related cancers. The next stage is to gain an understanding of the biological processes involved from c-Myc activation, to tumour growth and finally to islet tumour involution. To do this, the relatively new technique of microarray analysis will be used. This powerful method allows changes in gene expression over the whole genome to be analysed, giving an insight into the genetic pathways that occur downstream of c-Myc activation. It is hoped that some understanding of any biological processes pertinent to carcinogenesis can be studied in more detail, with the eventual aim of such studies being an eventual gene specific therapy for cancer.

For more information, please see Dr. Michael Khan's website.

 

Mathematics and Computing:

"The Use of Topological Proteomics in the Study of Pancreatic Cancer."

Supervised by David Epstein with additional help from Abhir Bhalerao.

The growth of cells within the body is carefully mediated by the precise interactions of a variety of proteins. Occasionally, degenerative genetic changes may occur, disrupting this precise protein interplay which can lead to errors in the regular growth process. This can often lead to excessive growth, with cells no longer controlled by regular signalling pathways. Excessive cellular growth and an inhibition of natural defensive processes (such as apoptosis) can lead to the production of cancerous tumours. Unfortunately, the exact genetic changes that occur in the early onset of tumour development are not yet fully understood. A new technique in topological proteomics has been developed by Meltec, and it is hoped that this will aid in research by providing a topological mapping of protein interactions within tissue samples. This is a new technique, and as such is not necessarily free of errors. The process involves the incubation of various fluorescently stained antibodies to the tissue, each designed to bind to an individual protein. Fluorescence microscopy is used to capture an image showing the presence of a specific protein, and the sample is washed and bleached to remove fluorescent molecules before incubation of the next antibody. A sequence of fluorescent images is produced that can be combined and viewed in parallel at a later stage. It is possible that we may see movement of the tissue sample between staining cycles, be it due to washing, bleaching, incubation or, more likely, mechanical vibrations. This would result in misalignment of the sequential images preventing meaningful comparison of successive protein images. In this paper, a method of image registration is discussed for the alignment of pancreatic tissue images stained using the MELK process. Samples are taken from a cancer model, allowing for activation and deactivation of the oncogene c-Myc, known to result in the onset and subsequent regression of insulinoma in the pancreatic islets. It is hoped that this method of topological proteomics, together with results obtained from microarray studies, immunohistochemical staining and regular proteomics, will allow an insight into genetic pathways and the interactions of proteins involved during the early stages of c-Myc induced insulinoma growth. The MELK process will aid in understanding the role that these genes play in the early onset of cancer, leading to the possibility of a gene specific therapy, and an eventual cure for cancerous activity.

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