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Quantitative regulatory genomics - Mirko Francesconi

Why are individuals different? We address this fundamental question by studying both genetic and non-genetic sources of phenotypic variation, using both genome-wide computational and experimental systems biology approaches in model organisms. In particular, we are interested in understanding how gene expression is regulated in space and time to contribute to phenotypic variation.

 

Addressing big questions with big data

In my lab we address fundamental biological questions using big data integration and modelling, and experimental approaches. We especially focus on genome-wide gene expression dynamics - including at single-cell and single-individual level - as a multidimensional information-rich intermediate phenotype and as a powerful generator of mechanistic hypotheses (Francesconi and Lehner 2015, Bulteau and Francesconi 2022).

Gene regulation in space and time

Many disease causing mutations do not change gene sequences but when, where and how much genes are expressed. While we understand to a good extent the impact mutations in coding sequences we still do not understand the impact of genetic variation on regulation of gene expression. How can we predict the impact of genetic variation on gene regulation? What are the determinants of gene expression in space and time? These are some of the questions we are addressing in my lab (Francesconi and Lehner 2014). 

Why are genetically identical individuals phenotypically different?

Genetically identical individuals are often phenotypically different. For example, identical twins are often discordant for common genetic diseases such as schizophrenia. Beside the genome, one obvious factor that can impact phenotypes, is the environment in which organisms are born and develop. However, studies in genetically identical model organisms, where the environment is carefully controlled, highlight extensive inter-individual phenotypic variation. Understanding the causes, the consequences and the mechanisms underlining this phenotypic variation is therefore is one of the current main open question in biology. And one of the questions we are interested in my lab (Perez, Francesconi et. al, 2017). More recently we discovered that sensory information about the social environment perceived by the nervous system of the parents is transmitted to the progeny impacting their germline development and minimum generation time (Perez et al. 2021). This is one of few demonstrated examples where a physiologically relevant sensory information perceived by the nervous system of an animal is transmitted to the progeny impacting their fitness. We are currently investigating the mechanisms of signal transmission and interpretation in the progeny and exploring other phenotypic traits such as behaviour are impacted by neuronal perception of the environment in the previous generation.