Title of project
Detecting tissue-specific microRNA secretion in hyperglycemia using bio-orthogonal RNA tracing and nano-sensors
Abstract
Introduction
Extracellular RNA (exRNA) has emerged as a critical mediator of intercellular communication. Various tissues release specific RNA species into the bloodstream, yet the regulatory mechanisms and tissue origins of these secreted RNAs under pathophysiological conditions, such as impaired glucose metabolism, remain unclear. Understanding these mechanisms could lead to novel biomarkers for metabolic disorders.
Objectives
This project aims to:
- Apply a novel RNA labeling technique to identify RNA species secreted by different tissues in response to elevated glucose levels.
- Develop nano-sensors for the rapid and quantitative detection of these tissue-enriched and secreted RNAs.
- Validate the findings through clinical samples from the Danish Childhood Obesity Biobank, focusing on RNA markers linked to the progression of impaired glucose metabolism in pediatric obesity.
Methods
The study employs cutting-edge RNA labeling and tracking techniques alongside advanced nanosensor development to measure exRNA levels. I will use advanced ex vivo mouse tissue culture and human donor tissue with lentiviral delivery of a specific esterase (BS2) under cell-specific promoter combined with BS2-activated acylating reagents that I will synthesize myself. Validation of nanosensor quantification will be compared with RT-qPCR assays using samples from the Danish Childhood Obesity Biobank, specifically targeting children with obesity to establish biomarkers for metabolic deterioration. I will explore the functional significance of specific exRNAs in collaboration with my strategic partner, Anand Hardikar, at Western Sydney University.
Perspectives
This research will provide insights into exRNA secretion mechanisms and contribute to the development of cost-effective diagnostic tools, potentially revolutionizing the clinical monitoring of glucose metabolism-related disorders.
