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Institute
Lens epithelium derived growth factor (LEDGF), is known to be overexpressed in different solid cancers and cancer cell lines but is also involved in acquired immunodeficiency syndrome (AIDS) and diverse inflammatory diseases. Due to its chromatin-binding ability, it acts as a transcriptional coactivator, promoting anti-apoptotic pathways leading to increased tumor aggressiveness and chemotherapy resistance. In this thesis, the role of LEDGF in laryngeal cancer cells was investigated. Thus, a knock-out of LEDGF in HEp-2 cells was successfully generated by CRISPR/Cas9 technology. Moreover, LEDGF-deficient HEp-2 cells exhibited a decreased proliferation and migration, as well as an increased chemotherapy sensitivity towards topoisomerase II inhibitor etoposide. The DNA damage response was in more detail investigated, where LEDGF depleted cells showed a drastic reduction in the recruitment of downstream damage-response related proteins, more precisely replication protein A subunit of 32kDa (RPA32), and an increased amount of DNA fragmentation, highlighting the role of LEDGF in homology-directed DNA repair.
In addition, a efficient method was established to allow genomic tagging of LEDGF at its C-terminus with EGFP which enables the monitoring of LEDGF in living cells. Therefore, an efficient Cas9-mediated DNA DSB induction was supplemented with a DNA template containing homology arms to the C-terminus as well as the EGFP sequence to allow homology-directed repair. Subsequently, EGFP-expressing cells were FACS sorted and single cells expanded. Almost all test clones showed a homozygous genotype for LEDGF-EGFP fusion which exhibited the typical nuclear pattern of LEDGF.
Conservation of heritage sites is an integral part of history and culture through which new generations can learn about their forefathers education, professionalism, cultural characteristics as well as their civilization. Almost all countries of the world tend to conserve their historical sites for their own generations and travellers from abroad. Despite Bangladeshs economy is becoming stronger, it is not paying enough attention to the development of archaeology to conserve its heritage sites. Unlike many other developing countries, Bangladesh tends to considers it a luxury to preserve it’s heritage sites. It is mainly because of the scarcity of land. The tiny country has a huge population (about 180 million), the density of which is perhaps the highest in the world.
Apart from some very significant heritage sites, most others are awfully neglected. Lack of education and awareness among the respective local people and other stakeholders are also responsible for most of the heritage sites facing threats of demolition, vandalism, losing authenticity and integrity.
Panamnagar, the case study for this thesis paper, is not apart from the above scenario. It is the last surviving intake city of lost Bengal. The place witnessed Mughal emperor, British rule, the partition of Bengal, Liberation war of Bangladesh, Hindu-Muslim riot, illegal habitation of people, forced eviction and abundance. The historic city went through lots of historical events and is still standing as a testimony to the golden era of Bengal. Currently, this heritage site is facing multiple threats to its existence and authenticity. The city is vacated by the authority - the Department of Archaeology. But as the local people are not aware of the historic value of the site, they are not at all cooperating with the authority. Meanwhile, the authority is trying to incorporate adaptive reuse of the site to give life to it again and collect revenue for the maintenance. But they are doing it without assessing the cultural significance of the site properly, which could be a potential threat for the authenticity of the heritage site. Thus, this paper has focused on assessing the cultural significance of the heritage site, with a hope that it will help the authority to make policy decisions for the conservation of the site more cautiously. To assess the cultural significance properly, history and architectural significance are described briefly. A site analysis has been conducted to understand the current site condition properly. The paper concludes with statements in support of the cultural significance of Panamnagar site and recommends appropriate conservation tools to sustain its significance.