From chemical design to synthetic biology: two complementary strategies to tackle the BBB

Back from a very rewarding stay in Yale, Pol already has new ideas in mind to overcome the barrier that protects the brain and makes it so difficult to design drugs to cure neurological diseases.

PhD student Pol Arranz (Gelida, 1987) has just come back from a three-month stay in Yale.  His eyes shine with excitement when he tells in vivo about it. He works in Ernest Giralt’s Design, Synthesis and Structure of Peptides and Proteins Lab, and is particularly focussed on peptide shuttles that can cross the Blood-Brain Barrier (BBB), one of the lab’s fortes. About a year ago, Pol took part in a B-Debate dedicated to Synthetic Biology.  “I was already fascinated by the subject and I wanted to find out more,” say Pol. In that event, he heard Farren Isaacs, one of the authorities in the field, and he decided to pursue a stay in his lab, at Yale. “Ernest strongly encourages us to look for short-term placements in another lab in another country during our graduate studies,” explains Pol. “He gives us full freedom to decide something that makes scientific sense to us.” The idea of spending some time in Yale became a reality after Pol went to Paris in December last year and met Isaacs in person at a conference. “I introduced myself to him and he accepted to host me in his lab.”

Arranz believed that his expertise was complementary to what he wanted to learn in Isaacs’ lab. “To improve our peptides and make them more efficient and stable, here in the lab we introduce non-natural amino acids into the amino acid sequence, ” he explains. “At Yale, they can use the cellular machinery for this. I already knew the chemical approach and I wanted to learn about the biological method,” he concludes.

The Catalan biochemist had a good curriculum to present to his American colleagues. After working on a special class of so-called passive diffusion BBB shuttles, called phenylprolines, he participated in pioneering research on another type of shuttle, this time molecules that are able to actively transport larger molecules into the brain. He is also working on the use of these peptides to enable a gene therapy to cure Friedreich’s Ataxia, which affects the central nervous system.

In June, when I got to Isaac’s Lab, he let me check out all his projects. I finally decided to collaborate with one of his PhDs on a completely new project. They work in a very different type of application to those I am used to, and it was stimulating to start thinking differently,” he adds.

After Arranz has defended  his thesis at the end of the year, the idea is to return to Yale to continue the project as a postdoc. “The research environment there was fantastic,” he says. “In such a competitive and front-line lab, I was expecting a lot of pressure. But I was pleasantly surprised by the friendly atmosphere and the collaborative spirit. I felt a bit like how feel in my lab at IRB Barcelona!” He made some good friends there. “I had planned to visit Boston and New York during my stay, and when I told some of my lab mates what I had in mind, some of them decided to accompany me to show me around. We also went climbing very often. I ended up feeling part of the group.”