Signe Mathiasen

Project title

Signaling properties of ADGRL3, an adhesion GPCR putatively activated by mechanical transsynaptic forces

What is your project about?

This project is focused on building a basic understanding of a new and exciting receptor, called ADGRL3. ADGRL3 is expressed in the brain and implicated in ADHD and other psychiatric disorders that involve dopamine dysfunction, such as schizophrenia. The project will, among other things, map ADGRL3's basic biological functions such as how the receptor is activated, what downstream signaling cascades are turned on as a consequence of activation as well as what cellular response ADGRL3 activation leads to. This is important in order to understand the role of the receptor in, for example, ADHD and such knowledge can potentially contribute to designing improved medical strategies against neuropsychiatric disorders.

How did you become interested in your particular field of research?

During my bachelor's degree, I was introduced to a number of exciting biophysical examples of protein 'machinery', and in particular G protein coupled receptors (GPCR), a class of proteins that bind signal molecules on the outside of the cell to start a series of signaling processes inside the cell, caught my attention.  I have been fascinated by ADGRL3 since the beginning of my postdoc in New York (Columbia University Medical Center). ADGRL3 compose a giant protein structure that combines several functions. On the one hand, it can bridge two neurons to stabilize the contact zone between neurons (the synapse), and on the other hand, it can control signal cascades inside the cell through its transmembrane G protein coupled receptor (GPCR) domain.

What are the scientific challenges and perspectives in your project?

ADGRL3 has been associated with increased risk of ADHD in human genetic studies, and implicated in neuropsychiatric disorders that involve dysfunctional dopamine signaling, as for example schizophrenia. ADGRL3 is therefore a new potential drug target in such diseases, but in order to design strategies for targeting ADGRL3, one will have to map the basic functions of the receptor, such as e.g. how it is activated, and I hope to be able to contribute to that. In addition, ADGRL3 belongs to a class of proteins, ‘adhesion GPCRs’, which are generally understudied, and new knowledge about the activation mechanism of these proteins will be groundbreaking for the adhesion GPCR field in general.

What is your estimate of the impact, which your project may have to society in the long term?

I hope my research can help provide a better understanding of how ADGRL3 can be used as a drug target and what role this receptor has in neuropsychiatric diseases, as well as to help develop pioneering methods in the field of adhesion GPCR research.

Which impact do you expect the Sapere Aude programme will have on your career as a researcher?

It is a huge honor to be awarded a Sapere Aude grant. This is the first large grant I have received in Denmark and it means that I can start establishing my research and group at the University of Copenhagen. I am really looking forward to get started after 6 years in New York.

Background and personal life

I live with my husband and two lovely children aged 3 and 0.5 in Frederiksberg. From 2014-2020, I have lived and worked at Columbia University (New York). I love being with my family and friends and once in a while when have some time to myself I go swimming or to a yoga class.