June 14, 2005 | David F. Coppedge

Cell Wonders Accelerate

Scientific papers on cell biology continue to uncover amazing things as techniques improve to peer into the workings of these units of life.  Here are our Top Ten from the last few weeks:

  1. Immunity Tunes:  A press release from Johns Hopkins talked about how, unlike other cells, immune cells undergo a “dizzying loop of activity” to generate huge varieties of antibodies through recombination.  They liken the regulator of the recombination process to a band leader directing a jam session.  (Emphasis added in all instances.)
  2. Oxygen Sensor:  “Cell’s Power Plants Also Sense Low Oxygen” announced a report from Howard Hughes Medical Institute.  In summary, “Researchers have produced the strongest evidence yet that mitochondria – the organelles that generate energy to power the cell – also monitor oxygen concentration in the cell.  If oxygen slips below a critical threshold, the mitochondrial ‘sensor’ triggers protective responses to promote survival.”  Controlling oxygen levels is important.  Both too little and too much can be deadly, not only to the cell, but to the whole organism.
  3. Reverse Gear:  Nature1 June 9 talked about the myosin monorail trains that ride the microtubule rails.  Out of the myosin superfamily of motor proteins, consisting of 18 classes, they were curious how Myosin VI is bidirectional, unlike most of its siblings.  They studied its “lever arm,” “power stroke” and “converter” but did not come up with a final model of how it works.  “Undoubtedly, this unique myosin family member has yet more surprises to reveal,” they concluded.
  4. Transporters:  Aussie biologists talked about protein transport into mitochondrial membranes in Current Biology.2  Since there are two membranes, similar to those in chloroplasts (see 01/01/2005 story), there are two squads of transporters to get the cargo in and out.  Named TOM and TIM for translocons of the outer and inner membranes, these are “a series of molecular machines” that know how to sort and authenticate objects needing to pass the gates.  They envisioned an “entropic spring” mechanism that can help get the cargo passed through “no apparent input of energy.”  This type of mechanism is “an emerging theme in biology” that harnesses the disordered motion of molecules to provide binding flexibility and low energy cost to accomplish “a range of functions.”  “The TIM23 complex is a smart machine,” they say, describing its ability to grab a piece of cargo, insert it, respond to a stop-transfer signal and reject it, or pass the cargo to the next machine complex.
  5. Tissue Triage:  Another paper in Current Biology3 discussed how epidermal cells repair damage.  The phylogeny of this ability was a puzzle: “Amazingly, while the eyes and hearts of Drosophila and mammals are constructed in entirely different ways and are morphologically quite distinct, their development appears to be under the control of similar master-regulatory transcription factors,” they said.  These operations on two vastly different types of organisms cannot be homologous, they suggest; they must be due to convergent evolution.  However the repair mechanism arose, it involves signaling and a cascade of coordinated events involving molecular machines.  The result?  A stitch in time, and wounds that are self-healing.  This is another “conserved repair response,” they say, meaning that it is found early in the history of life with little change since.
  6. Quality Control:  A press release from Yale described a protein that “recognizes misfolded RNAs, creating a RNA quality control system for cells.”
  7. Kissing Chromosomes:  A news story in Nature4 sheds light on a mystery of gene regulation.  We all know chromosomes come in pairs, but how do the genes on each member get expressed together when they are separated by distance?  Out of the “many strategies to orchestrate gene activation or repression” in the cell’s bag of tricks, “A three-dimensional examination of gene regulation suggests that portions from different chromosomes ‘communicate’ with each other, and bring related genes together in the nucleus to coordinate their expression.”  It’s nice that the spouses are on speaking terms.  “Such inter-chromosomal communication has been suspected for some time,” Dimitris Kioussis said, “but this is the first evidence that it actually takes place.”  Our understanding of gene regulation has changed from a linear view “to an appreciation that genes are associated with groups of proteins, forming multimolecular complexes,” he said.  We’re going to have to see the process not just in snapshots or just a movie: “Is it time to go 4D?” he jests with implicit seriousness.  No one knows how the chromosomes are brought together.  “How do genes find their appropriate location in the nucleus of a cell, and how are genes that must be expressed herded into active neighbourhoods?” he asks (see “Spaghetti in a Basketball,” 07/28/2004).  Whatever the mechanism, “These remarkable findings will puzzle us for some time to come.”
  8. Inter-Agency Coordination:  Cities have fire departments, police departments, ambulances, highway patrol, disaster response teams and other agencies that sometimes have overlapping duties.  Cells do, too.  There are multiple repair mechanisms able to respond to different kinds of DNA damage.  Scientists writing in Molecular Cell5 discussed what is known about how they coordinate their actions during the emergency repair called TLS (trans-lesion DNA synthesis): “The process requires multiple polymerase switching events during which the high-fidelity DNA polymerase in the replication machinery arrested at the primer terminus is replaced by one or more polymerases that are specialized for TLS.  When replicative bypass is fully completed, the primer terminus is once again occupied by high-fidelity polymerases in the replicative machinery.”  It sounds like the first-aid squad knows how and when to patch up things enough to get the patient to the surgeon.
  9. Texas Tech:  Scientists in Texas, publishing in Cell,6 found another multi-talented molecular machine.  The rotor part of the V-type ATP synthase (see 02/24/2003 entry) does more than just help acidify vesicles.  It also has “an independent function in membrane fusion,” they found.  It is essential in the process of exocytosis – what neurons do to transmit their messages.  They found that mutant embryos had severe defects in synaptic transmission of nerve signals.  (This was found in fruit flies.)  By the way, the other form of this rotary motor, the F-type ATP synthase, was called “The World’s Smallest Wind-Up Toy” by Richard Berry in Current Biology.7  Researchers have figured out how to make the motor turn, using magnets.  He thinks scientists are on the verge of figuring out how the F0 rotor converts proton flow into torque.
  10. Ultimate Spa:  Last but not least, scientists at the Salk Institute last month announced a surprising solution to the puzzle of how embryos start their left-right orientation.  An “embryonic body wash” operated by cilia sweeps chemical signals across the embryo: “the foundations for the basic left-right body plan are laid by a microscopic ‘pump’ on the outer surface of the embryo’s underside that wafts chemical messengers over to the left side of the body.  This sets up a chemical concentration gradient that tells stem cells how and where to develop.”  The cilia rotate at a precise 40-degree angle to generate a current over the embryo.  The original paper in Cell contains movies of the action.

1Menetrey et al., “The structure of the myosin VI motor reveals the mechanism of directionality reversal,” Nature 435, 779-785 (9 June 2005) | doi: 10.1038/nature03592.
2Perry and Lithgow, “Protein Targeting: Entropy, Energetics and Modular Machines,” Current Biology, Vol 15, R423-R425, 7 June 2005.
3Stramer and Martin, “Cell Biology: Master Regulators of Sealing and Healing,” Current Biology, Vol 15, R425-R427, 7 June 2005.
4Dimitris Kioussis, “Gene regulation: Kissing chromosomes,” Nature 435, 579-580 (2 June 2005) | doi: 10.1038/435579a.
5Friedberg et al., “Trading Places: How Do DNA Polymerases Switch during Translesion DNA Synthesis?” Molecular Cell, Volume 18, Issue 5, 27 May 2005, Pages 499-505, doi:10.1016/j.molcel.2005.03.032.
6Heisinger et al., “The v-ATPase V0 Subunit a1 Is Required for a Late Step in Synaptic Vesicle Exocytosis in Drosophila,” Cell, Volume 121, Issue 4, 20 May 2005, Pages 607-620, doi:10.1016/j.cell.2005.03.012.
7Richard Berry, “ATP Synthesis: The World’s Smallest Wind-Up Toy,” Current Biology, Vol 15, R385-R387, 24 May 2005.

Sometimes we just have to rub it in: these are just a few samples from the flood of literature coming out each week in cell biology, biochemistry and genetics (check out another example from 01/27/2003).  A little overkill is needed once in awhile, a quadruple jolt of caffeine to make the Darwinists wake up and smell the coffee.  Almost none of these papers even mention evolution, and the ones that do only assume it: e.g., Myosin VI “might have evolved to provide unique kinetic characteristics that are potentially important for a reverse-directed motor.”  Do they really expect anyone to believe that any more?
    The papers are filled, on the other hand, with design language: motors, machines, mechanisms, coordinated action, synergy, regulators, signaling, strategies and much more.  This illustrates how useless Darwinism is; with apologies to Dobzhansky, nothing in biology makes sense in the light of evolution.  Intelligent design, by contrast – whether explicit or implicit – yields profound insights.  Let ID be the golden cord to show us the way out of the dark labyrinth where Charlie misled us long ago into the lair of the Minotaur, naturalism.

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