In an ambitious two-year postdoc project, Malte Thodberg aims to map gene regulation in the gastrointestinal tract and create a catalogue of gene regulation to discover whether genetic changes associated with type 2 diabetes play a particular role in the microbiota-gut-brain axis

When we eat, the gastrointestinal system sends hormone and nerve signals to the brain, resulting in changes in our appetite and behaviour. This communication between the gastrointestinal system and the brain is important for regulating metabolism and is called the microbiota-gut-brain axis.

Genetic changes in cells in the microbiota-gut-brain axis are likely to affect the risk of a person developing type 2 diabetes. We have already identified a number of genetic changes associated with the development of type 2 diabetes, discovered through Genome Wide Association Studies. However, this approach does not show in which cells and tissues the genetic changes play a special role.

“In particular, we do not know to what extent genetic changes play a role in signalling via the microbiota-gut-brain axis, since the gastrointestinal tract is a complex organ divided into many regions and cell types,” says Malte Thodberg, who received his PhD in Bioinformatics from University of Copenhagen in 2018.

He aims to remedy this situation in his study by mapping gene regulation down to the single cell level and creating a catalogue of cell types in the gastrointestinal tract and their gene regulation.

“We will use single-cell mapping to analyse DNA sequence variants associated with increased risk of type 2 diabetes via changes in the gastrointestinal tract. This will enable us to find new molecular targets for clinical intervention and calculate a more accurate cell-specific genetic risk profile for the development of type 2 diabetes,” says Malte Thodberg, who gained extensive experience in the area of analysing sequencing data while working on his PhD and in a previous postdoc position.

Three sequencing methods on biopsies from the gastrointestinal tract should ensure thorough mapping of gene regulation at the single cell level
Malte Thodberg will use three different single cell sequencing analyses to ensure a thorough mapping of the cells’ gene regulation: RNA sequencing, which measures gene expression; ATAC sequencing, which measures open chromatin; and ChIP sequencing, which measures epigenetic changes.

The sequenced cells will come from biopsies taken from different sites in the gastrointestinal tract from a minimum of 20 donors. Partners at Bispebjerg Hospital will facilitate access to these biopsies.

Malte Thodberg will also collaborate with the Blood Bank at Rigshospitalet. He will also work for two months at the Big Data Institute of Oxford University, United Kingdom, where Cecilia Lindgren, Professor and Director of the Oxford Big Data Institute, will share her world-leading expertise in the type of advanced data analysis that Malte Thodberg needs for his project.

Malte Thodberg will be based at the Novo Nordisk Foundation Center for Basic Metabolic Research at University of Copenhagen. Here he will work under the leadership of Professor Torben Hansen, who is internationally recognised for his work on exploring the hereditary causes of diabetes. 

Contact
Malte Thodberg
E-mail: malte.thodberg@sund.ku.dk
Tel: +45 31 51 10 14

Danish Diabetes Academy
Managing Director Tore Christiansen
E-mail: tore.christiansen@rsyd.dk
Tel: +45 29 64 67 64

/By Project Manager Nina Jensen, Danish Diabetes Academy