26 April, 2007

Metaphorical Molecular Riddle

The trapeze artists are at war, yet the net result is peace.

They cry at each other, 120 times over, "NACTI! NACTI! TINAC! NACTI!"

Individual soldiers came and went, more remain than gone.

While their weapons repeat beyond their shield 5 to 6 times.

Their weakness lies in the happy 2 plus upon which all depend.

What system is this?

25 April, 2007


It's like one of those old Popeye cartoons.

Popeye and Bluto are fighting. p53 and Mdm2 are fighting.

Popeye and Bluto are fighting for Olive Oyl.

p53 and Mdm2 are fighting for the fate of the cell. It is an epic battle played out daily all over the world, being won and lost every single moment. p53's purpose is to make sure that all of a cell's DNA is properly replicated and not mutated before cell division may proceed. Mdm2 opposes p53 to keep it from clamping down too tightly upon cell division.

Although it may seem that p53 is antagonistic to life by opposing cell division, it is essential for our survival. In multicellular eukaryotic organisms such as we usually are, cell division is tightly regulated. Too little cell division and the organism doesn't work whereas too much cell division results in uncontrolled cell proliferation (also called cancer). So thank your p53. And Mdm2.

22 April, 2007

Multiple Sclerosis

On any other day one would find them standing close by, snug up against each other and glued in place to create an impenetrable wall. But today something is odd. As blood pulses, pushing at them from one side, they begin to lose grip, just a little bit, but it's enough. The endothelial cells panic. Normally it is their given purpose to protect the precious brain matter on the other side of the capillary, and they are failing. Collectively, they don't know what is going on, so they signal for help individually. Cell surface proteins are changed from cadherins to integrins and cytokines are wafted out into the blood, calling for macrophages to come and see what is wrong.

That was their first mistake.

As they always do, the macrophages quickly come sailing down the bloodstream, slowing down and rolling along the sides of the capillary until they reach the distressed endothelial cells, where they squeeze themselves between the loosened cells. Normally, macrophages cannot penetrate the tight barrier presented by the endothelial cells in the blood-brain barrier, but this is different.

Letting them cross was their second mistake, but it was one they could hardly help since something seems to be wrong with their adhesion factors in the first place.

Inside the densely packed brain matter, the macrophages are confused. This is tissue they've never seen before, it is strange and alien to them, usually closed off but suddenly opened wide for them to see. The macrophages know that that which is strange and alien means danger to the organism, and as such, they mount their normal innate immune response. The funny-tasting brain matter is blasted with oxidative chemicals as yet more cytokines are wafted out through the bloodstream.

Soon the side of the weakened capillary is crawling with immune cells. In addition to macrophages, there are now monocytes, neutrophils, natural killer cells, and dendritic cells. All that the former can do is blast the weird tissue with yet more chemicals and try to eat it, but it is the latter cells, the dendritic cells, whose appearance is most ominous.

The dendritic cells busily set up shop, ingesting pieces of the brain matter and swooping back out in the bloodstream. There they sneak out of postcapillary venules into lymph nodes and other lymphatic organs and, like mother birds regurgitating food for their young, spit those pieces of brain matter back up so that the developing, naive T cells and B cells can see and and feel it and memorize one simple fact: THIS IS OUR ENEMY!

The T cells and B cells go wild and proliferate all over the place. The B cells swell with antigens against the brain matter, and so does the blood serum. The T cells migrate to the site of weakened blood-brain barrier and join the macrophages and others in bombarding the brain matter with pro-inflammatory chemicals in a concerted effort to destroy it. The B cells' antigens mark the brain matter for destruction, and phagocytosis sets in.

The oligodendrocytes of the brain matter are confused, hurt, and reeling from the sudden onslaught of the immune system. Collectively, they teeter on the edge between survival and apoptosis, and unfortunately many of them fall to apoptosis, disrupting the normal course of electrical signalling in that part of the brain.

Eventually, the endothelial cells of the blood-brain barrier recover and rejoin to once again deny the immune system access to the brain matter. So the immune system lurks outside, ready and muttering to itself, while the brain matter inside ineffectually tries to heal itself, recovering to some degree, but nonetheless still bearing deep scars.

13 April, 2007

Cubitus Interruptus

Pity poor Cubitus interruptus. If you are here, and reading something such as these words, then you can identify with poor, scrawny Cubitus. Every day Cubitus was held down by the other big kids, like Fused, and backed up against a microtubule as he was beaten again and again, degraded time after time. All that Cubitus ever wanted to do was run away to the nucleus to play with his imaginary friend, CSL, but alas, Fused kept him away every time.

The all-seeing Patched saw all that happened to poor Cubitus, every time, and did nothing. Patched only sat there imperiously, watching with a cold hard and an even colder grip on Smoothened's shoulder. You see, Smoothened had a kind heart, and would gladly have gone to help poor Cubitus by disrupting the bullying actions of Fused, but Patched restrained her.

Then one day Hedgehog came along. Hedgehog snuck up alongside Patched and all of a sudden sank his spines into Patched.

No one knows why Hedgehog did it.

Nonetheless, it gave Smoothened that one opportunity she needed, and she darted away and shoved Fused off of little Cubitus. Cubitus, finally free of Fused's blows, immediately darted away to the nucleus to frolic with his imaginary friend and was happy ever after.

Moral: Smoothened is nicer than you think. Patched is a bitch.

02 April, 2007

Signalling Poem 1

A steroid receptor receives
A protease cleaves

A ribosome makes
A proteasome breaks

GPCRs stimulate
Within the cAMP appelate
Although PDE hates
What adenylyl cyclase makes
Together they speak
In a molecular feat
Signals from outside to in

When one shoves the other
The other shoves back
Although the cAMP'd druther
Avoid the PDE hack
But a balance is made
And a signal is sent
Action potentials laid
Or secretory granules rent
And communication is.