Why? Because while lots of progress has been made in studying transcriptional control, still relatively little is known on how mRNA fate and resulting protein amount is defined. I believe, and have created proof of concept data, that such knowledge allows to create new models of human disease and ask treatment relevant questions form a completely new angle.
The importance of gene regulation in generating complex phenotypes is well illustrated by the observation that the number of protein-coding genes is almost the same in humans and nematode worms. Our lack of knowledge regarding the mechanisms that regulate gene expression in higher organisms means that we are unable to design animal models or regenerate tissue for disease treatment. We believe that an ability to control endogenous gene expression—limited to naturally-expressing cells in a gene’s physiological context, i.e. at the post-transcriptional level — would provide us a tool that can enhance our understanding of gene function and open new scientific, industrial, and therapeutic venues.
Our laboratory’s goal is to better understand the rules and parameters which define mRNA stability and efficiency of protein synthesis. For this we are currently creating anabolic/catabolic maps of mRNA/protein and applying bioinformatics analysis pipelines.
We have also already implemented conditional fine-tuning to endogenous gene expression levels, for example, through 3'UTR editing. Among other things, this tool allows us to address whether an elevation in the expression of given protein is desirable to model or treat a disease of interest. In 2017 our laboratory received an ERC Consolidator Grant on generating improved mouse models and treatment venues for Parkinson’s disease. This research lead to several surprising findings, both in the field of neurology with implications in better understanding schizophrenia and in molecular biology culminating in currently ongoing R2B project funded by Business Finland which aims to improve industrial protein production by implementing our unique knowledge on 3’UTRs.
Our laboratory uses cell lines, molecular biology tools, bioinformatics, genetic engineering in mouse models and subsequent analysis at the molecular, cellular, tissue, behavioral and electrophysiological levels. With a CRO we are also working to create a new small molecule drug to create the first knowledge-based precision medicine for schizophrenia sub-group which we recently identified. We are now further stratifying these patients by coordinating an ERANET NEURON research consortia 2022-2025.
We have also recently generated a new mouse model for long-segment Hirschsprung’s disease and for Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) and are currently involved in projects aiming to define better treatment and understanding of those disorders.