Combining in silico and in vivo approaches for understanding the evolution of transcription factor binding sites in Escherichia coli

• Grant number: 17/16783-5
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: November 01, 2017
• End date: April 30, 2018
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Rafael Silva Rocha
• Grantee: Cauã Antunes Westmann
• Supervisor: Orkun S. Soyer
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Warwick, England
• Associated to the scholarship: 16/05472-6 - Synthetic biology approaches to engineer/mine novel regulatory elements in bacteria, BP.MS

Abstract

Biological innovation at the molecular level is essential for promoting novel adaptation strategies in living organisms. Thus, studying the dynamics of this process is a key step for predicting and engineering novel biological functions. In the context of transcriptional regulation, innovation drives the diversity of cellular decision-making processes by acting on both trans and cis-regulatory elements. Here, we focus on the study of Transcription Factor Binding Sites (TFBSs), which can rapidly evolve in the genome due to spontaneous mutations. We propose a novel framework for exploring the evolutionary principles underlying transcriptional innovation in bacteria using Escherichia coli as a model. Based on preliminary results, we have hypothesized bacterial TFBSs are somewhat promiscuous, having the potential to be recognized by more than one transcription factor. Thus, the main goals of this project are: (i) to test the current hypothesis by in silico exploration of a large set of TFBSs from E. coli and (ii) to merge computational results with experimental data generated by the candidate in order to provide a general model for the evolution of TFBSs in bacteria. Our ultimate goal is to use this iterative cycle between in silico and in vivo approaches for both understanding transcriptional systems and generating principles of design for engineering novel regulatory functions in bacteria. We highlight the Dr. Orkun Soyer´s laboratory, where the current projected will be developed, is exactly at the interface between computational and experimental approaches for deciphering evolutionary principles of biological systems, providing a prosperous environment for the candidate to develop his skills and research. This project will also set new computational frameworks that will be later implemented in Ribeirão Preto with an important impact in the main project of the group.