A potential pan-cancer diagnostic utilizing DNA methylation landscapes

This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.

Supervisor – Dr Abu Sinaa.sina@uq.edu.au

DNA methylation is a key epigenetic modification which involves the addition of a methyl group to the 5 position of cytosine nucleotides. Eukaryotic cell’s DNA maintains a distinct methylation landscape to regulate gene expression pathways and maintain genomic stability. However, in cancer, this methylation landscape experiences a significant reprogramming with a net loss of global DNA methylation at the intergenic regions of the genome together with a concomitant increase in methylcytosine levels at clustered CpG sites involved in regulatory roles (e.g., selective hyper-methylation at promoter regions). We have recently discovered a consequence of genome-wide epigenetic reprogramming induced by cancer, which has been overlooked to date: that the key physicochemical properties of purified genomic DNA are fundamentally different between normal and cancer genomes. We found that the purified genomic DNA from normal cells had a greater tendency towards aggregation in aqueous solutions than genomic DNA from cancer cells. This appears to be caused by the hydrophobic properties of methylcytosines, leading to different self-assembly of DNA polymer in solution, depending on the levels and patterning of methylcytosines across the genome. I also found that the solution properties of cancer and normal epigenomes influenced their affinity towards bare gold surfaces. In addition to the solvation properties, gold-DNA interaction was also modulated by the higher affinity of methylcytosines towards gold in comparison to the regular cytosines, and as a function of their clustered or dispersed patterning across the genome, which in turn, could determine the pathological state of the DNA. Thus, we hypothesized that the unique methylation landscape displayed by most cancerous epigenomes which we referred to as “Methylscape” may potentially serve as a universal cancer biomarker. Consequently, we developed a one-step pan-cancer detection technology based on interfacial bio-sensing without the need for sequencing, chemical/enzymatic treatment of samples, and PCR amplification procedure

This proposal aims to test the cancer detection accuracy of this novel method in a larger cohort of clinical samples using an automated chip to allow rapid sample multiplexing. It simultaneously aims to develop a new strategy to investigate the methylation-based allele frequency (MAF) in the blood samples from earlier to the later stage of cancer.

Preferred educational background

Applications will be judged on a competitive basis taking into account the applicant's previous academic record, publication record, honours and awards, and employment history.

The applicant should have: biochemistry and molecular biology background with interest in nanotechnology and microfluidics. Theoretical Knowledge of DNA Methylation and Cancer. Experience in working in a molecular biology lab and be familiar with standard molecular biology methods such as DNA extraction, PCR reaction, Cell culture, etc.

*The successful candidate must commence by Research Quarter 4, 2022. You should apply at least 3 months prior to the research quarter commencement date. International applicants may need to apply much earlier for visa reasons.

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