INTERVIEW

Dino Moras

Interviewed by Laura Spinney

Posted September 28, 2001 · Issue 111

Background

Biography
Dino Moras trained as a chemist in Strasbourg, France, but came to structural biology through his postdoctoral work in the lab of crystallographer Michael Rossmann at Purdue University, Indiana. On his return to France in the late 1970s he joined the Institute of Molecular and Cellular Biology at the Centre National de la Recherche Scientifique (CNRS) in Strasbourg, where he set to work on the problem of the translation of the genetic code. One of the main challenges was to understand the function of the aminoacyl-transfer RNA synthetases (aaRS), enzymes crucial for catalyzing this translation. In 1990 his group was the first to report that there are actually two structurally and functionally distinct classes of aaRS. In 1994 he moved to his present post at the Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), CNRS-INSERM-University Louis Pasteur, also in Strasbourg, where he says the main emphasis is on biomedical research, and its implications for human health.

Who has most inspired and/or influenced your work?

In the early 1970s very few protein structures were known, and so it was reading one of the early papers in which one of these structures was published that really impressed me and persuaded me to choose structural biology. I knew very little about the field, though, and it was by others' recommendations that I went to Michael Rossmann's lab. [Rossmann is perhaps best known for recognizing the so-called Rossmann Fold, or nucleotide-binding fold, as a feature common to several different enzymes]. I owe a lot to Michael Rossmann. He really was the one who made me passionate about the subject. He works mainly on the structure of viruses these days.

What was your best experiment?

My work on synthetases, certainly. In the early 1980s the question being asked was how do aaRS recognize their corresponding tRNA in order to synthesize the correct amino acid in the protein being constructed. We contributed to the answer by identifying two different classes of aaRS that act as catalysts for different chemical reactions, and we were also the first group to describe the crystal structure of a complex formed by the second class of aaRS. Before that I was known for my work on the structure of tRNA. But more recently, I would point to our studies of nuclear receptors and in particular the structures of their ligand-binding domains. This is important because it explains how hormones activate these receptors, which are crucial for the regulation of cell function. On the application side, of course, knowing the structures of these receptors and the complexes they form could lead to the design of better drugs - for instance, ones that interact with estrogen receptors.

Which scientific idea (yours or others') do you regret the most?

I have been lucky in that way, I have no serious regrets. But it took me a long time to get the first structure of a complex formed by aaRS - practically 15 years. We made it eventually, with a lot of perseverance. All the big projects I have worked on have taken longer than I expected. With the nuclear receptors, for instance, it took me five years to get the first structure of a ligand-binding domain.

What is the greatest unanswered scientific question?

I hope to work for as long as I can on the explanation of the regulation of transcription. How does nature regulate gene expression? This is the question that fascinates me and has done for a long time. I'm not sure that I will see the outcome but I will try to get closer, and to learn from others. We are beginning to be able to see how these interactions move, and especially how they move so fast within a cell. We are explaining, bit by bit, protein recognition, hormone action, and so on. Gradually we are completing the picture. One major question is how fast the cell's translation machinery can pick up the right position in the genome to get a message through as quickly as it does. But this is a level of complexity that we cannot even approach right now. First we need to understand how it works at all. And of course when we understand how it works normally we will have some insight into what happens when it goes wrong.

What are your scientific plans for the next 5 years?

My work on the ligand-binding domain of a nuclear receptor is just the first step. Now I'm going to work on the full receptors and the interactions between these receptors and other transcription factors, which is the next step in the reaction.

What are the qualities of a successful researcher?

You need luck, certainly, but also intuition and adaptability. For me a good scientist is always open to the facts and doesn't try to force them. He or she follows the experiments, adapts as quickly as possible, and perseveres.

If you could work with any scientist (historical or current), who would it be?

I have a great admiration for many people, but that doesn't mean I could work with them! I was very impressed by Max Perutz [who won the Nobel Prize in Chemistry in 1962 for his work on the structures of globular proteins], whom I have met a few times but not enough.