Claes Wadelius – Genomic Analysis of Gene Regulation
The principles for how genes are activated and inactivated are known but from a genomic perspective our knowledge is very limited. Each cell type has a unique set of active genes that are regulated by the action of a collection of the 2000 transcription factors and other nuclear proteins that bind the DNA molecule.
Methods to study gene regulation
We use the latest high-resolution methods, like CUT&RUN and ChIP-seq, to study where a given protein binds to DNA along the whole genome to regulate the activity of individual genes. To study the 3D structure of the genome we use methods like 4C. we also use variants of the gene scissors CRISPR to activate and turn off individual gene regulatory elements and genes.
This type of large-scale analysis has challenged the traditional view of gene organization. There are multiple regions that activate and inactive a gene in a given tissue. The human genome codes for around 20 000 genes but current international data indicates that they are controlled by close to 1 000 000 regulatory elements so much work remains to understand how different genes are regulated in health and disease.
Revealing mechanisms behind diseases
These studies generate massive amounts of data and in order to fully explore the information we develop new informatics strategies and collaborate with specialists in the field. The methods can be used to reveal the mechanisms for common diseases and cancer. We have started to explore this in liver cells and immune cells and have found hundreds of regulatory variants that likely explain association to common metabolic and autoimmune diseases. We have also characterized a large collection of regulatory variants that are excellent candidates to contribute to cancer.