Characterization of Intron Retention and its role in cancer regulation using bioinformatics
Role
Principal Investigator
Description
In this project, the aim is to gain new insights into mechanisms underlying a largely overlooked form of alternative splicing, intron retention (IR), with impacts on gene regulation, cell physiology and disease. IR is a widespread phenomenon in which the splicing machinery fails to excise introns from primary transcripts. This can lead to diverse downstream effects, such as the synthesis of novel peptides, RNA decay, or the suppression of protein or non-coding RNA synthesis. Recently, IR was described as widespread mechanism of tumor suppressor inactivation, which suggests a significant contribution to cancer emergence and progression. In this project, machine-learning approaches and pattern recognition algorithms will be used to unravel the molecular causes for IR events and to determine the extent to which IR is conserved in other species. The integration and mining of massive amounts of RNA-sequencing and epigenomics data, including leukemia patient data, will generate deeper insights into IR, its origins, mechanisms of regulation, and its role in cancer. There is evidence that IR can be used to enhance disease outcome predictions. Therefore, one aim of this project is to derive an IR-based biomarker for leukemia. Understanding how IR events are triggered and suppressed will open the way for exploring novel avenues for cancer treatment. For this purpose I aim to design and implement a cancer genomics analysis pipeline to uncover alternative splicing events, including IR, that may lead to cancer pathogenesis and progression. Moreover, an algorithm for the prediction of IR occurrences and possible pathogenic consequences will be developed. In summary, the proposed aims of this project should lead to advancements in understanding cancer pathogenesis which may ultimately give rise to patient-tailored designs of therapeutic regimens. This project will contribute to our understanding of gene regulation with particular emphasis in leukemia pathogenesis.
Date
01 Jan 2017 - 31 Dec 2020
Project Type
FELLOWSHIP
Keywords
N/A
Funding Body
National Health and Medical Research Council (NHMRC)
Amount
318768
Project Team
N/A