Cell Wonders Accelerate
06/14/2005 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:
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.)
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.
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.
Transporters: Aussie biologists talked about protein
transport into mitochondrial membranes in Current
Biology.2 Since there are two membranes, similar to
those in chloroplasts, 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.
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.
Quality Control: A press release from Yale
described a protein that ¡°recognizes misfolded RNAs, creating a
RNA quality control system for cells.¡±
Kissing Chromosomes: A news story in
Nature4 shed 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,¡± Dmitris 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. Whatever the mechanism, ¡°These remarkable findings
will puzzle us for some time to come.¡±
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.
Texas Tech: Scientists in Texas, publishing in
Cell,6 found another multi-talented molecular
machine. The rotor part of the V-type ATP synthase 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.
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.
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 is Darwinism for the study of life.
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.