Sabrina Ruhrmann,

Hjelt Grant Holder 2023,

Lund University.

Epigenetic Editing - a way to a personalized treatment approach in type 2diabetes (T2D)

The number of people affected by diabetes is rapidly increasing worldwide. Type 2 diabetes (T2D) largely contributes to this increase and individuals with T2D usually face high blood sugar levels. To balance our blood sugar level the hormone Insulin is necessary and Insulin target tissues like muscles need to be able to take up glucose in response to Insulin. Overweight

and no physical exercise can lead to insulin resistance (where the uptake of glucose is not any longer possible e.g. in our muscles) and almost all individuals with T2D show Insulin resistance.

Our DNA only explains a small proportion of how T2D is passed on from parents to their children (also described as the so called “missing heritability”). Given the crucial role of diet and physical exercise in the development of T2D, mechanisms mediating the interaction of those factors with our genes should be of particular importance when trying to explain how T2D develops.

Epigenetic mechanisms fulfil this criterion. Epigenetics is the study of how e.g. the environment and/or our behavior can affect the expression of our genes without changing our DNA. The fact that epigenetic changes do not change our DNA unlike genetic changes gives us the opportunity to “correct“ them.

We are here trying to discover epigenetic changes that cause T2D. We will create small molecules called guideRNAs (gRNAs) that will help us to search for those epigenetic changes using the so called inactivated gene scissor system, CRISPR-dCas9. We will further try to also 'correct' these epigenetic changes to explore if epigenetic mechanisms may be targeted for a more patient specific treatment of T2D in the future.