Enebie moved from his homeland on the Spanish island of Gran Canaria to The Netherlands to be with his Dutch partner in 2016, and was lucky to find that the first Molecular Life Sciences study in English had just been launched in Nijmegen. "I studied chemical engineering at home, which was 90% engineering. I wanted to study more chemistry and I've been fascinated by biology since I was a kid. So the study in Nijmegen was perfect."
He went on to get a Master's degree in molecular life sciences with (among others) Kim Bonger, who offered him a PhD position right after. "I knew little about immunology but I took a leap in the dark. To make chemistry useful to understand life is the most fascinating thing to me."
Exploding cells
Enebie studies a relatively newly discovered way that neutrophils (white blood cells that play a crucial role in the innate immune system) attack pathogens. In a process called NETosis, the entire neutrophil explodes and spreads its contents to form extracellular fibers that trap and kill pathogens. But, as Enebie explains: "We don't know how NETosis affects the rest of the body. In large amounts it may do damage. And we don't have a lot a of ways to study the process which involves a lot of enzymes. I was hired to make tools to study the process of NETosis in live cells and tissues."
Enebie developed and synthesized probes with a fluorophore that only lights up when it is bound to a specific enzyme. While such probes were known, these are the first ones that are applied to NETosis-related enzymes. The first paper is about to be published, in which the researchers show that their probes can be used to detect myeloperoxidase enzyme activity in live cells under wash-free conditions.
A key step is to test the probes on human blood samples as opposed to standardized cell lines. Enebie learned how to collect and prepare human donor blood for this. To convince potential healthy donors he promises them an image of their own white blood cells. "People love it! It really helps," claims Enebie. "I'm proud of the images, they look very cool. The probes help to see that there is something actually going on. It is regular confocal fluorescent microscopy but if you pay attention, you can make a very nice picture. And a picture is worth a 1000 words."
Studying brain tissue
Over the next months, using the probes he developed Enebie will study the interaction of neutrophils with amyloid proteins, which form aggregates and plaques in the brain and are associated with Alzheimer's. Some amyloids are shown to trigger NETosis, but the question is how much and via which pathways. "Ultimately my goal is to use the probes to study brain tissue from deceased Alzheimer's patients."
Even though Enebie does not have an ICI partner to cooperate with, which he regrets, he's grateful for the program ICI offers. "The workshops and courses and conferences are very good, I have attended most of them. I met a lot of people and have contacts that I would not have had without ICI.