Better understanding of genome function and disease physiology

As a Wallenberg Scholar, Tuuli Lappalainen wants to increase our understanding of the genetic architecture that gives rise to complex genetic diseases, diseases caused by a combination of multiple gene variants and environmental influences.

Lappalainen and her research team want to map the molecular mechanisms that influence human traits and disease development through genetic variation. 

Through large-scale studies, such as genome-wide association studies, researchers have been able to develop a catalogue of sites in the genome - genetic loci - that are linked to human traits and diseases. However, the majority of these genetic loci are found in the non-coding regions of the genome that are often of unknown function, making the underlying mechanisms of the associations unknown, hindering the ability to understand the origin of a trait or disease from a molecular biology perspective. This is an obstacle for development of effective and specific treatments. 

Develop standardised methodology

Over the last 10-15 years, the goal of human genetic research has therefore shifted from identifying genetic loci associated with a trait in population data, to understanding the underlying molecular mechanisms.
Lappalainen and her research team want to elucidate underlying mechanisms by mapping genes found in the associated locus, exploring how they regulate the rest of the genome, and mapping how the effect of the gene variants in the locus differ in different cells and cell stages. 

The aim is to develop a standardised methodology that is generalisable and enables studies of the link between genetic associations and the molecular mechanisms in other diseases. The team will combine approaches from population genetics and molecular biology. The main goal of the project is to bridge the gap between findings from large population association studies and experimental molecular biology research, by bringing together the traditionally distinct approaches.

The results aim to contribute to a better understanding of genome function and disease physiology, thereby enabling the identification of molecular targets for interventions that can help advance precision medicine.