The Ferrell lab is working to understand the design principles of biochemical switches, timers, and oscillators, especially those that control the cell cycle.
The drawing above is of a 2-cell Xenopus laevis embryo, from Nieuwkoop and Faber (1994) via Xenbase. Xenopus embryos and extracts are particularly powerful systems for quantitative studies of cell cycle regulation, and much of the lab's work makes use of these systems.
* * * NEWS * * *
May 19 2016: Our own Julia Kamenz has been selected as a speaker for this year's Cold Spring Harbor Cell Cycle meeting. Julia will speak this Saturday (May 21) about her work on protein dephosphorylation during mitotic exit.
May 13 2016: We have a new paper out on thresholds and negative cooperativity. Here's a quick summary:
In the 1960's, Dan Koshland introduced the idea of "negative cooperativity" in the function of proteins with multiple subunits. In negative cooperativity, the binding of one ligand makes it harder for a second ligand to bind. The standard theory on negative cooperativity says that the higher the negative cooperativity, the more graded the receptor's response.
It turns out there is a little algebraic shortcut built into the standard theory--effectively it is an assumption that the binding of ligand molecules to receptors has no significant impact on the concentration of free ligand. In many situations, especially intracellular signaling, this assumption does not hold.
If one re-derives the theory without this little shortcut, the results are different, and kind of remarkable. Negative cooperativity can endow a receptor's response with a marked threshold, making it so there will be no response until the ligand concentration is higher than the receptor concentration. Sang Hoon Ha tested the new theory with a series of synthetic biology experiments, using DNA oligonucleotides to represent the receptor and ligand species and manipulating the cooperativity of their binding. The results are in beautiful agreement with the new theory.
The paper has just been published in Science (click here). Congratulations Sang Hoon!
Apr 29 2016: Jim is just back from the University of Texas Southwestern, where he presented the 16th annual Rupert E. Billingham Lecture in Cell Biology. Jim talked about trigger waves in intracellular communication.
Mar 2016: Bye bye! As of April 1, our own Lendert Gelens leaves Stanford Chemical and Systems Biology and begins as an Asst. Professor at the University of Leuven in Belgium. He will head the Dynamics in Biological Systems (DiBS) lab. We are all looking forward to watching this exceptionally able young scientist become one of the leading lights in quantitative biology. Good luck, Lendert!
Feb 2016: Jim speaks at the Biophysical Society's 60th Annual Meeting in the Synthetic Biology Symposium, which is Sun Feb 28 from 8:15-10:15 AM. So does Stanford Chemical and Systems Biology's own Mary Teruel. More info? Click here.
Feb 2016: Jim's review on perfect adaptation was just published in Cell Systems. The article disusses the Holy Trinity of adaptation mechanisms—negative feedback, incoherent feedforward regulation, and state-dependent inactivation—as well as a new twist on negative feedback recently proposed by Mustafa Khammash and his colleagues (click here). As important as at is to understand how signaling systems are turned on, it is nice to be getting a comprehensive picture of what nature does to ensure that they get turned back off.
Feb 2016: We are just back from the Winter q-Bio meeting in Honolulu. Lendert Gelens gave a talk about his and Graham Anderson's unpublished work on waves of mitosis in embryos. Jim presented Xianrui Cheng's unpublished work on apoptotic trigger waves (Hawaii is a good place for waves!) and Sanghoon Ha's unpublished work on negative cooperativity. Ferrell lab alumna Silvia Santos also spoke, presenting new stuff on the temporal modularity of mitosis in mammalian cells. A splendid time was had by all!
Feb 2016: Please check out the latest paper from Sanghoon Ha and Sun Young Kim, just published in Cell Reports. The paper takes on the question of why it is that the Suc1/Cks proteins, components of the cyclin B-Cdk1 complex, seem to both promote and inhibit cell cycle progression. The answer lies in the prozone effect, where adaptors like Cks proteins can promote complex formation at substoichiometric concentrations, but then inhibit complex formation at suprastoichiometric concentrations. The paper is a nice combination of theory, proof-of-principle experiments, and in vitro studies of cyclin B1-Cdk1-Cks2 biochemistry.
Nov 2015: The EMBL Symposium on "Biological Oscillators: Design, Mechanism, and Function" took place Nov 12-14 at EMBL in Heidelberg. Jim spoke about how the reactions underpinning a biological oscillator can determine the spatial organization of the oscillations.
Oct 2015: Congratulations to Graham Anderson, who successfully defended his Ph.D. thesis, in fine style, on Oct 30. The title of his presentation was "Embryonic Division Waves Develop Autonomously and Precede Proper Mesoderm Induction".
Oct 2015: Congratulations to Dr. Lendert Gelens, whose talk at the "Physics of Living Matter" symposium in Cambridge UK was awarded the "Best Young Researcher Prize". Dr. Gelens spoke on the spatial coordination of development in Xenopus embryos subject to temperature perturbations. The work was done in collaboration with Graham Anderson from the Ferrell lab and K. C. Huang from the Dept. of Bioengineering.