Life Sciences & Biotechnology
Title : | studying the role of Helicobacter pylori in regulating the m6A methylation in gastric cancer |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Rajesh Kumari, University Of Allahabad, Uttar Pradesh |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | singhrr87@gmail.com |
Equipments : | Nanodrop
BOD Incubator
Cell culture biosafety cabinet
Cell Culture CO2 Incubator
Deep Freezer -20
Optical Inverted Research microscope |
Details
Executive Summary : | Helicobacter pylori (H. pylori) is a helical-shaped, flagellated microaerophilic pathogen that colonizes the human stomach. The complex host-pathogen interaction and drug resistance development is still ongoing research for eradicating H. pylori infection. N6-methyladenosine (m6A) is the most prevalent epitranscriptomic modification which regulates RNA biology including processing, nuclear export, stability, translation and degradation in both coding and noncoding RNAs. The m6A modification is catalyzed by the m6A methyl transferase complex (also called m6A writers), having methyltransferase like-3 (METTL3), METTL14 and Wilms' tumour 1-associating protein (WTAP) as key components. The m6A methylation is removed by demethylase (also called m6A eraser), including alkB homolog 5, RNA demethylase (ALKBH5) and fat mass and obesity-related transcript (FTO). The m6A modification is recognized by the YTH domain containing proteins like YTHDF1-3 etc. which are termed as "m6A readers". The writers, erasers and readers together constitute the m6A methylation machinery. The role of m6A methylation in many infectious diseases is reported recently. Plasmodium yoelii changes the expression of m6A methylation machinery enzymes to modulate m6A mRNA methylation of the host spleen. similarly, infection of Cryptosporidium parvum down-regulates the expression of both demethylases ALKBH5 and FTO thus reducing global m6A levels in intestinal epithelial cells. In viral infections, viral RNA gets methylated by the host and is important in viral replication. For example, m6A methylation of the genome of flaviviridae RNA viruses and HIV-1 gRNA promotes increased translation of viral RNAs and thus helps in viral replication. The m6A methylation plays an essential role in the initiation and progression of different types of cancer, including gastric cancer. Gastric cancer is one of the leading causes of cancer-related deaths worldwide. High expression of YTHDF1 is a strong risk factor for developing gastric cancer and overexpression of METTL3 has a significant role in promoting cell proliferation. The role of m6A in infection biology and gastric cancer is well documented but no studies are available on the H. pylori-mediated gastric cancer. We will exploit both in-vitro and in-vivo systems to understand the role of H. pylori infection in modulating host m6A methylation using infection studies, Western blotting, m6A dot blot, m6A ELIsA, m6A methyl immunoprecipitation RNA sequencing, cell proliferation assays and computational analysis (gene ontology) etc. For the first time, this proposal aims to address the existing knowledge gap on how H. pylori modulates m6A methylation, and whether H. pylori mRNAs get m6A methylated or not by the host. This study will enhance our understanding of the role of m6A methylation regulation during H. pylori infection and could be helpful in designing m6A-based antimicrobial therapeutics. |
Total Budget (INR): | 48,05,830 |
Organizations involved