Frej Tulin

Presented by Frederick R. Cross
M.S., KTH Royal Institute of Technology
Exploration of Cell Cycle-specific Essential Gene Functions in the Microbial Plant Chlamydomonas reinhardtii

My laboratory has worked in the budding yeast model system for some years. Many labs have devoted a lot of effort over the years to understand this one organism as well as possible, resulting in a large amount of information as well as very advanced techniques. Although this approach could seem to reflect an undue interest in budding yeast entirely disproportionate to its importance aside from making beer, people stuck to it because it provided huge insights into animal cell biology, as a result of evolutionary conservation of basic functions. Microbes are generally much faster and easier to work with than are animals, so this strategy turned out to be very effective.

Despite these advantages, Frej Tulin wanted to work in a different organism, the green alga Chlamydomonas. His reason was that while budding yeast is a surprisingly good model for animal cells, it is much less good for the hugely important plant kingdom — a consequence of early evolutionary divergence. Frej reasoned that experiments in the microbial alga could yield insights into fundamental plant cell biology, much as yeast had for animals.

In principle this was a good idea, but there were two critical problems. First, next to none of the advanced methods available for budding yeast worked in Chlamydomonas; second, even the methods that did work were completely unfamiliar to me or to anyone in the lab, or indeed in the university. So the first thing Frej did was to spend a month in the lab of Susan Dutcher at Washington University, to learn the basics of dealing with Chlamydomonas. He returned knowing enough at least to get started.

The project he wanted to do was to identify and analyze most or all of the genes involved in control of the cell division cycle. This task was accomplished in the yeast system only over decades of work by a great number of researchers. So the proposal was to develop new methods for Chlamydomonas in a lab that had never worked on the organism, and to carry out a project that had taken great resources and thousands of researchers 20 years or so. This proposal was a bit less crazy than it sounds, because of recent advances in robotics for microbiology, and new DNA sequencing technologies that can greatly speed gene identification. Still, it was a very tall order. It would be necessary to collect and analyze huge numbers of mutants, while at the same time inventing new methods for this collection and analysis — a really challenging lift-yourself-by-your-bootstraps problem.

Ultimately, the project succeeded remarkably well. The list of genes is well on the way to being truly comprehensive, there is clear functional information as to the role played in the cell cycle by more than 50 genes, and, most important, there is clear conservation of much of what Frej has learned about in higher plants — justifying the fundamental assumption of the project. Thus, genes known for years to exist in higher plants, with no clearly assigned role in the cell cycle or perhaps anything else, now for the first time can be analyzed functionally in a rapid experimental system.

I’d like to take this opportunity to reinforce comments made by the graduate student speakers earlier — the strong commitment of the Rockefeller program to allowing students to work independently on subjects of interest, without undue worrying about financial support, was essential in allowing Frej to carry out this project. This is a unique aspect of the program, and we are grateful to all the people who make this possible.

Frej now plans to move on to work directly in higher plants, focusing on issues of development and chromosome organization that are not accessible from the alga system.