James Ferrell

Last updated
James E. Ferrell
James E. Ferrell.jpg
Born (1955-11-03) November 3, 1955 (age 65)
Alma mater Stanford University, Williams College
TitleProfessor of Chemical and Systems Biology
Scientific career
Institutions Stanford University School of Medicine
Website James E. Ferrell Lab at Stanford

James Ellsworth Ferrell (born November 3, 1955) is an American systems biologist. He is a Professor of Chemical and Systems Biology and Biochemistry at Stanford University School of Medicine. He was Chair of the Dept. of Chemical and Systems Biology from its inception in 2006 until 2011. [1]

Contents

Education

Ferrell was an undergraduate at Williams College, majoring in Physics, Chemistry, and Mathematics, and graduated in 1976. He received his Ph.D. degree in Chemistry from Stanford University in 1984 for work in the laboratory of Wray H. Huestis on the control of red cell shape, and received his M.D. degree from Stanford in 1986. He carried out postdoctoral work on signal transduction in the laboratory of G. Steven Martin at UC Berkeley.[ citation needed ]

Research

Through studies of Xenopus laevis oocyte maturation, Ferrell showed how graded changes in the inductive stimulus progesterone are converted into irreversible, all-or-none changes in MAP kinase activity, cyclin-dependent kinase activity, and cell fate. [2] [3] [4] [5] [6] These studies helped demonstrate how ultrasensitivity, positive feedback, and bistability can allow cells to switch between discrete states. [7]

Subsequent work from the Ferrell lab [8] and others [9] demonstrated that the cell cycle transition between interphase and mitosis is regulated by a bistable switch, and that the Xenopus early embryonic cell cycle operates like a relaxation oscillator. [10] [11] [12] These findings helped validate earlier theoretical predictions and modeling studies. [13] [14]

Recently the Ferrell lab showed that the mitotic state can propagate through Xenopus cytoplasm via trigger waves, waves of Cdk1 activity that spread faster and farther than the Cdk1 protein molecules can diffuse. [15] [16] [17] They also showed that apoptosis propagates through cytoplasm by trigger waves; the "speed of death" is about 2 mm per hour. [18] [19]

Related Research Articles

Bistability

In a dynamical system, bistability means the system has two stable equilibrium states. Something that is bistable can be resting in either of two states. An example of a mechanical device which is bistable is a light switch. The switch lever is designed to rest in the "on" or "off" position, but not between the two. Bistable behavior can occur in mechanical linkages, electronic circuits, nonlinear optical systems, chemical reactions, and physiological and biological systems.

<i>Xenopus</i> Genus of amphibians

Xenopus is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-known species of this genus are Xenopus laevis and Xenopus tropicalis, which are commonly studied as model organisms for developmental biology, cell biology, toxicology, neuroscience and for modelling human disease and birth defects.

Germ cell Gamete-producing cell

A germ cell is any biological cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they undergo meiosis, followed by cellular differentiation into mature gametes, either eggs or sperm. Unlike animals, plants do not have germ cells designated in early development. Instead, germ cells can arise from somatic cells in the adult, such as the floral meristem of flowering plants.

An oocyte, oöcyte, ovocyte, or rarely ocyte, is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in the ovary during female gametogenesis. The female germ cells produce a primordial germ cell (PGC), which then undergoes mitosis, forming oogonia. During oogenesis, the oogonia become primary oocytes. An oocyte is a form of genetic material that can be collected for cryoconservation.

Spindle checkpoint

The spindle checkpoint, also known as the metaphase-to-anaphase transition, the spindle assembly checkpoint (SAC), or the mitotic checkpoint, is a cell cycle checkpoint during mitosis or meiosis that prevents the separation of the duplicated chromosomes (anaphase) until each chromosome is properly attached to the spindle. To achieve proper segregation, the two kinetochores on the sister chromatids must be attached to opposite spindle poles. Only this pattern of attachment will ensure that each daughter cell receives one copy of the chromosome. The defining biochemical feature of this checkpoint is the stimulation of the anaphase-promoting complex by M-phase cyclin-CDK complexes, which in turn causes the proteolytic destruction of cyclins and proteins that hold the sister chromatids together.

John Gurdon English developmental biologist (born 1933)

Sir John Bertrand Gurdon is a British developmental biologist. He is best known for his pioneering research in nuclear transplantation and cloning. He was awarded the Lasker Award in 2009. In 2012, he and Shinya Yamanaka were awarded the Nobel Prize for Physiology or Medicine for the discovery that mature cells can be converted to stem cells.

G2 phase, Gap 2 phase, or Growth 2 phase, is the third subphase of interphase in the cell cycle directly preceding mitosis. It follows the successful completion of S phase, during which the cell’s DNA is replicated. G2 phase ends with the onset of prophase, the first phase of mitosis in which the cell’s chromatin condenses into chromosomes.

A circadian clock, or circadian oscillator, is a biochemical oscillator that cycles with a stable phase and is synchronized with solar time.

Restriction point

The restriction point (R), also known as the Start or G1/S checkpoint, is a cell cycle checkpoint in the G1 phase of the animal cell cycle at which the cell becomes "committed" to the cell cycle, and after which extracellular signals are no longer required to stimulate proliferation. The defining biochemical feature of the restriction point is the activation of G1/S- and S-phase cyclin-CDK complexes, which in turn phosphorylate proteins that initiate DNA replication, centrosome duplication, and other early cell cycle events. It is one of three main cell cycle checkpoints, the other two being the G2-M DNA damage checkpoint and the spindle checkpoint.

Calcium signaling

Calcium signaling is the use of calcium ions (Ca2+) to communicate and drive intracellular processes often as a step in signal transduction. Ca2+ is important for cellular signalling, for once it enters the cytosol of the cytoplasm it exerts allosteric regulatory effects on many enzymes and proteins. Ca2+ can act in signal transduction resulting from activation of ion channels or as a second messenger caused by indirect signal transduction pathways such as G protein-coupled receptors.

Cell cycle checkpoint

Cell cycle checkpoints are control mechanisms in the eukaryotic cell cycle which ensure its proper progression. Each checkpoint serves as a potential termination point along the cell cycle, during which the conditions of the cell are assessed, with progression through the various phases of the cell cycle occurring only when favorable conditions are met. There are many checkpoints in the cell cycle, but the three major ones are: the G1 checkpoint, also known as the Start or restriction checkpoint or Major Checkpoint; the G2/M checkpoint; and the metaphase-to-anaphase transition, also known as the spindle checkpoint. Progression through these checkpoints is largely determined by the activation of cyclin-dependent kinases by regulatory protein subunits called cyclins, different forms of which are produced at each stage of the cell cycle to control the specific events that occur therein.

Wee1

Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe. Wee1 has a molecular mass of 96 kDa and is a key regulator of cell cycle progression. It influences cell size by inhibiting the entry into mitosis, through inhibiting Cdk1. Wee1 has homologues in many other organisms, including mammals.

Mechanosensitive channels, mechanosensitive ion channels or stretch-gated ion channels (not to be confused with mechanoreceptors). They are present in the membranes of organisms from the three domains of life: bacteria, archaea, and eukarya. They are the sensors for a number of systems including the senses of touch, hearing and balance, as well as participating in cardiovascular regulation and osmotic homeostasis (e.g. thirst). The channels vary in selectivity for the permeating ions from nonselective between anions and cations in bacteria, to cation selective allowing passage Ca2+, K+ and Na+ in eukaryotes, and highly selective K+ channels in bacteria and eukaryotes.

A series of biochemical switches control transitions between and within the various phases of the cell cycle. The cell cycle is a series of complex, ordered, sequential events that control how a single cell divides into two cells, and involves several different phases. The phases include the G1 and G2 phases, DNA replication or S phase, and the actual process of cell division, mitosis or M phase. During the M phase, the chromosomes separate and cytokinesis occurs.

Maternal to zygotic transition is the stage in embryonic development during which development comes under the exclusive control of the zygotic genome rather than the maternal (egg) genome. The egg contains stored maternal genetic material mRNA which controls embryo development until the onset of MZT. After MZT the diploid embryo takes over genetic control. This requires both zygotic genome activation (ZGA) and degradation of maternal products. This process is important because it is the first time that the new embryonic genome is utilized and the paternal and maternal genomes are used in combination. The zygotic genome now drives embryo development.

G2-M DNA damage checkpoint

The G2-M DNA damage checkpoint is an important cell cycle checkpoint in eukaryotic organisms that ensures that cells don't initiate mitosis until damaged or incompletely replicated DNA is sufficiently repaired. Cells which have a defective G2-M checkpoint, if they enter M phase before repairing their DNA, it leads to apoptosis or death after cell division. The defining biochemical feature of this checkpoint is the activation of M-phase cyclin-CDK complexes, which phosphorylate proteins that promote spindle assembly and bring the cell to metaphase.

Ultrasensitivity

In molecular biology, ultrasensitivity describes an output response that is more sensitive to stimulus change than the hyperbolic Michaelis-Menten response. Ultrasensitivity is one of the biochemical switches in the cell cycle and has been implicated in a number of important cellular events, including exiting G2 cell cycle arrests in Xenopus laevis oocytes, a stage to which the cell or organism would not want to return.

Temporal feedback, also referred to as interlinked or interlocked feedback, is a biological regulatory motif in which fast and slow positive feedback loops are interlinked to create "all or none" switches. This interlinking produces separate, adjustable activation and de-activation times. This type of feedback is thought to be important in cellular processes in which an "all or none" decision is a necessary response to a specific input. The mitotic trigger, polarization in budding yeast, mammalian calcium signal transduction, EGF receptor signaling, platelet activation, and Xenopus oocyte maturation are examples for interlinked fast and slow multiple positive feedback systems.

Mitotic Exit is an important transition point that signifies the end of mitosis and the onset of new G1 phase for a cell, and the cell needs to rely on specific control mechanisms to ensure that once it exits mitosis, it never returns to mitosis until it has gone through G1, S, and G2 phases and passed all the necessary checkpoints. Many factors including cyclins, cyclin-dependent kinases (CDKs), ubiquitin ligases, inhibitors of cyclin-dependent kinases, and reversible phosphorylations regulate mitotic exit to ensure that cell cycle events occur in correct order with fewest errors. The end of mitosis is characterized by spindle breakdown, shortened kinetochore microtubules, and pronounced outgrowth of astral (non-kinetochore) microtubules. For a normal eukaryotic cell, mitotic exit is irreversible.

The Novak-Tyson Model is a non-linear dynamics framework developed in the context of cell-cycle control by Bela Novak and John J. Tyson. It is a prevalent theoretical model that describes a hysteretic, bistable bifurcation of which many biological systems have been shown to express.

References

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  2. Huang, C. Y; Ferrell Jr, J. E (1996). "Ultrasensitivity in the mitogen-activated protein kinase cascade". Proceedings of the National Academy of Sciences of the United States of America. 93 (19): 10078–83. Bibcode:1996PNAS...9310078H. doi: 10.1073/pnas.93.19.10078 . PMC   38339 . PMID   8816754.
  3. Ferrell Jr, J. E; Machleder, E. M (1998). "The Biochemical Basis of an All-or-None Cell Fate Switch in Xenopus Oocytes". Science. 280 (5365): 895–8. Bibcode:1998Sci...280..895F. doi:10.1126/science.280.5365.895. PMID   9572732.
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  5. Xiong, Wen; Ferrell, James E (2003). "A positive-feedback-based bistable 'memory module' that governs a cell fate decision". Nature. 426 (6965): 460–5. Bibcode:2003Natur.426..460X. doi:10.1038/nature02089. PMID   14647386. S2CID   4396489.
  6. Sible, Jill C (2003). "Cell biology: Thanks for the memory". Nature. 426 (6965): 392–3. Bibcode:2003Natur.426..392S. doi: 10.1038/426392a . PMID   14647363.
  7. Ferrell, James E. (2002-04-01). "Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability". Current Opinion in Cell Biology. 14 (2): 140–148. doi:10.1016/S0955-0674(02)00314-9. ISSN   0955-0674. PMID   11891111.
  8. Pomerening, Joseph R; Sontag, Eduardo D; Ferrell, James E (2003). "Building a cell cycle oscillator: Hysteresis and bistability in the activation of Cdc2". Nature Cell Biology. 5 (4): 346–51. doi:10.1038/ncb954. PMID   12629549. S2CID   11047458.
  9. Sha, W; Moore, J; Chen, K; Lassaletta, A. D; Yi, C.-S; Tyson, J. J; Sible, J. C (2002). "Hysteresis drives cell-cycle transitions in Xenopus laevis egg extracts". Proceedings of the National Academy of Sciences. 100 (3): 975–80. doi: 10.1073/pnas.0235349100 . PMC   298711 . PMID   12509509.
  10. Pomerening, Joseph R; Kim, Sun Young; Ferrell, James E (2005). "Systems-Level Dissection of the Cell-Cycle Oscillator: Bypassing Positive Feedback Produces Damped Oscillations". Cell. 122 (4): 565–78. doi: 10.1016/j.cell.2005.06.016 . PMID   16122424.
  11. Cross, Frederick R; Siggia, Eric D (2005). "Shake It, Don't Break It: Positive Feedback and the Evolution of Oscillator Design". Developmental Cell. 9 (3): 309–10. doi: 10.1016/j.devcel.2005.08.006 . PMID   16139219.
  12. Adler, E. M; Gough, N. R; Ray, L. B (2005). "2005: Signaling Breakthroughs of the Year". Science Signaling. 2006 (316): eg1. doi:10.1126/stke.3162006eg1. PMID   16391177. S2CID   45634327.
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  14. Goldbeter, A (1993). "Modeling the mitotic oscillator driving the cell division cycle". Comments on Theoretical Biology. 3: 75–107.
  15. Chang, Jeremy B; Ferrell Jr, James E (2013). "Mitotic trigger waves and the spatial coordination of the Xenopus cell cycle". Nature. 500 (7464): 603–7. Bibcode:2013Natur.500..603C. doi:10.1038/nature12321. PMC   3758429 . PMID   23863935.
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  18. Cheng, Xianrui; Ferrell, James E. (2018-08-10). "Apoptosis propagates through the cytoplasm as trigger waves". Science. 361 (6402): 607–612. Bibcode:2018Sci...361..607C. doi:10.1126/science.aah4065. ISSN   0036-8075. PMC   6263143 . PMID   30093599.
  19. "For unwanted cells, death comes in waves | Cosmos". cosmosmagazine.com. 9 August 2018. Retrieved 2018-09-18.