Studying dimerization of Roco proteins in living cells
|PhD ceremony:||L.M. (Laura) Nederveen-Schippers, PhD|
|When:||April 05, 2022|
|Supervisor:||prof. dr. P.J.M. (Peter) van Haastert|
|Co-supervisor:||prof. dr. A. (Arjan) Kortholt|
|Where:||Academy building RUG|
|Faculty:||Science and Engineering|
This thesis describes the development of a method to measure protein pairing. This is important, among other things, for the protein LRRK2 (pronounced: lark-two) that is involved in Parkinson's Disease (PD). The fundamental insights resulting from this research contribute to the development of drugs that can inhibit or even prevent Parkinson's disease.
In a significant proportion of PD patients, the LRRK2 protein is hyperactive: it carries out a certain chemical reaction too often. Researchers would like to know how this protein activity is regulated and what it depends on so that it can be blocked. Previous experiments with disrupted cells indicated that it is important for protein activity that LRRK2 proteins are attached to each other in pairs ('dimers'). However, this had not yet been studied in living cells. The aim of my research was therefore to measure the pairing of LRRK2 in living cells.
Observing protein pairs in their biological context is not easy, however. In my dissertation, I adapted a certain microscope technique, in which the light intensity is calculated that each protein particle (provided with a green label) emits. Protein pairs are twice as bright as single proteins, and so we can now see in living cells (common lab cell lines) that LRRK2 'dimers' are indeed present. The next step is to block pairing with substances and observe this in living cells. Ultimately, Parkinson's drugs can be developed that counteract the LRRK2 hyperactivity and thus potentially halt the death of neurons and disease progression