Investigating Non-Canonical DNA 
Secondary Structures

i-Motifs

As we progressively shift our focus towards non-canonical DNA secondary structures, an understanding of their physiological significance becomes essential. One such structure is the i-motif or the cytosine-tetrad. i-Motifs are intercalated constructions formed by hemiprotonated cytosine-cytosinium base pairs. The nuclear formation of C-Quadruplexes and their prevalence in gene promoters, primarily those of oncogenes and proto-oncogenes, lead to speculations pertaining to the regulatory role of these structures. A series of studies have demonstrated that iMs can indeed act as switches for gene expression, wherein a regulatory value can be assigned to both iM folding/stabilisation and unfolding/destabilisation.

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We aim to dig deeper into the mechanism of action of these structures so as to unravel an additional layer of genomic regulation of gene expression.

Tumor Microenvironment

Cancer is a favorite of contemporary biologists, cancer plasticity being at the heart of present-day Oncology research. A major contributor to this plasticity is the Tumor Microenvironment that is also known to confer the much infamous drug resistance to cancer cells, hence making it a topic of utmost medical significance.  

Hypoxia

While Oxygen is very often considered a primary requirement for supporting higher order living organisms, it is also an element that, in theory, makes life highly improbable. Free Radical Chemistry of Ageing, by Denham Harman, is one of the most revered theory of ageing based on the concept of oxidative damage, thus supporting the prior statement. At the same time, a state of hypoxia is also directly correlated with accelerated senescence via an elaborate web of cellular signaling pathways. Thus, in simplest of terms, survival requires an intricately calculated physiological level of pO2 and this calculation becomes yet more complex when longevity is a consideration. Thus, physiological conditions/states that alter the well-balanced cellular oxygen availability demand our attention.