SENSOGENE - Cancer biosensors based on gene regulatory elements

Program for excellent projects of young researchers (PROMIS), Science Fund of the Republic of Serbia, 2020-2022

Principal Investigator: Aleksandra Nikolic, PhD, IMGGE

Participants from IMGGE: Sandra Dragicevic, PhD, Jovana Despotovic, Tamara Babic

Biosensor technologies have emerged as a promising tool for noninvasive and effective early detection of malignant disease, which remains a major unmet need in cancer management. Imaging techniques and traditional tumor biomarkers enable detection of tumors already developed to a significant extent and keep failing in detection of early stage tumors and premalignant lesions. This project will investigate the hypothesis that gene regulatory elements can sense malignancy at the molecular level and explore an innovative biosensor-based approach to cancer molecular diagnosis. The concept is based on universal property of gene regulatory elements to collect complex information from molecular network within the cell and translate it into a single quantitative output. The project will focus on a set of gene regulatory elements selected using open access databases and bioinformatics tools. Structural and functional analysis of gene regulatory elements will identify those with potential to be developed into biosensors and at the same time pinpoint molecular targets of interest for further research. The prototype of cancer biosensor will combine selected gene regulatory elements as biorecognition components with widely used genes for fluorescent proteins as signal transducers. Its diagnostic sensitivity will be tested using organoid cultures and clinical samples from patients with colorectal cancer. This type of cancer is an excellent model of a multistage tumor progression with morphologically and genetically well characterized premalignant lesions and malignant disease stages. The major expected output of the study is a molecular diagnostic tool developed for colorectal cancer with potential for further improvement and application across different types of malignant diseases. For the project team, the study will also enable introduction of novel methods, capacity building, improvement of international collaborations and strong foundation for future project applications.