"The breakthrough came with coffee, when a colleague advised me to add another ingredient"

“The breakthrough came with coffee, when a colleague advised me to add another ingredient”

Ricardo Thomas statue

I do basic research. That is, I’m interested in how things work, without looking for apps directly. My interest lies in the interaction between physics, biology and biophysics. I study mechanical aspects, eg how a cell divides: what kind of forces are involved and how does the cell generate them? In my research, we don’t look at living cells, but we build parts of cells ourselves. The looming point is the ability to create fully artificial cells, in order to better understand how real cells work.

The “failed” study in question was about the growth of fission yeast, a single-celled organism. These yeast cells grow by building up the cell wall, but only at the ends, so that they become an elongated cell. The materials needed for this growth are made in the middle of the cell and get to the right place via so-called microtubules, which are fast routes inside the cell. The question was: How could this growth material only end up at the ends?

Possible answer: Using a ‘molecular motor’. Such a motor runs over a microtube and carries with it the materials needed for cell growth. In this way, the dust ends up in the right place. We wanted to mimic this system, including moving to an artificial cell wall. This proved to be Difficult: The motor did not attach properly to the tube or left its load behind.We started this project in 2005, and only last year we had real success for the first time.

Statue of Marilyn Dogterum Inge Hoogland / KNAW

Marilyn DogeromeSculpture Inge Hoagland / KNAW

It didn’t work at the time. In 2007, an unexpected development occurred when I went on vacation in Rotterdam, in the laboratory of fellow researcher Anna Achmanova. During coffee breaks I would occasionally talk about the problem of molecular motors and growth materials, and Anna repeatedly advised me to add another ingredient, a certain type of cofactor molecule that she happened to study, but in animal cells. I have always rejected this idea, because I wanted to study the specific system with the engine and growth material. We thought that would only complicate the whole story.

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‘Of course we finally tried. Suddenly everything works. Even more surprisingly, the helper molecule alone turned out to be enough to make the system work. This was an important discovery, that the “simplified” system actually worked. We posted it very quickly in temper naturePrestigious magazine. For example, commenting on coffee suddenly led to a breakthrough.

This sounds nice, but we weren’t really interested in such a simplistic system. We are actually still working on the original goal, which is to recreate the load-transfer drive system on the cell wall. The idea from 2005 mainly resulted in a passing phase publication, but nonetheless our initial project came only a small step.

By adding something we didn’t care about at all, we discovered something that turned out to be important to many researchers in this field. Lots of things have to fail for something to work. Sharing such failures, even if only during a coffee break, is essential to the science: Ennick Slaughter, my predecessor as KNAW Chairman, said that fail forward“.

Marilyn Dogterm is Professor of Biophysics at Delft University of Technology. In 2018, she won the Spinoza Prize for her research. In addition, she has been the President of the Royal Dutch Academy of Arts and Sciences (KNAW) since 2020.

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