Monthly Archives: October 2012

Daily Roundup: Memory Modification

The latest in the spate of memory-related findings comes from the researchers at New York University and the University of California, Irvine. We’ve seen the effects of broad protein synthesis and how the interruption of the PKMZeta enzyme can cause long-term memory loss. Spatially, we’ve also seen how neurons can be stimulated to trigger memories. And at a lower level, scientists have identified how the Npsa4 gene is crucial for consolidating memories.

Now we have a little more information about how the molecules MAPK (mitogen-activated protein kinase) and PKA (cAMP-dependent protein kinase) are responsible for memory retention. According to the press release from NYU, PKA production increases for short term memory (30 minutes) in the sea slugs (really) being studied, and MAPK enters the picture when it comes to longer term memories. Interestingly, the creation of long-term memories involves both MAPK and PKA, with the former stimulating the latter’s involvement.

The abstracts that I found describing the proteins’ behavior were written several years ago, so I’m curious about the state of the research in memory modification and recall. I’d be interested to know what the authors think about the PKMZeta enzyme and how that plays into this research.

Additional info:

1. MAPK abstract on learning: http://learnmem.cshlp.org/content/12/5/538.short

2. PKA’s role in learning: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2632788/

The 2012 Nobel Prize in Chemistry

This year’s Nobel for Chemistry is awarded to Robert J. Lefkowitz and Brian K. Kobilka for their discovery of how the G-protein-coupled receptors (GPCR) work in our cells. This might sound a little finicky, but consider that the GPCR family accounts for half of pathways targeted by medical applications that do a whole host of things, from reducing pain to providing psychiatric relief to patients.

The impression I get from the excellent popular press release from nobelprizes.org is that the Nobel was awarded to the men who found ingenious ways of not only tracking the receptors’ work, but also in capturing the first images of how the protein actually functions within the cell.

GPCRs are so crucial because they provide one of the major ways that cells within our body interact with the external environment. Many intra-cellular activities occur in response to an external stimulus. For instance, you are startled by a sudden bang and your immediate instinct is to run away — that response is a result of adrenaline flooding your system, speeding up your heart but relaxing the pupils of your eyes. When adrenaline floods the system, it enters cells through the fatty acid layer of the cell and activates proteins that then go on to produce the correct physiological responses.

Normally I’d go ahead and explain the protein actions here, but in this case, I can’t do better than to refer to the press release, which is extremely clear and written with the lay person in mind.

Enjoy!

The 2012 Nobel Prize in Physics

This year’s Nobel has been awarded jointly to the French physicist Serge Haroche and American physicist David J. Wineland, for their independent usage of a special ultracool cavity and an ion trap respectively, to capture and study individual particles in their quantum states. This might sound extremely theoretical, but it could lead to the advancement of quantum computing, where computers can perform incredibly complicated algorithms in a fraction of the time they take to finish today.

All this is the result of the mind-bendingly odd physics that happens down at the atomic level, a quantum state that’s unlike anything we see in classical physics.

Quantum weirdness, to be honest, happens all the time: particles are naturally imbued with the ability to be both a, well, particle as well as a wave depending on how they’re measured and observed. But we don’t see cows, for instance, waving enthusiastically in fields because at the macro level these quirks of the quantum world cancel out. And they do so because of how the particles themselves interact with the external world.

In their natural, unobserved state — a sort of Platonic ideal, really — particles exist in a cloud of probable locations. They can’t really be pinned down, as Heisenberg discovered; they can be measured spatially or their velocities can be tracked, but never both simultaneously. This is said to be a superposition of states. This is where Schrodinger’s cat, poor creature, comes into the picture. The paradox, as the physicist put it, is that since every particle is in a state of flux, then so must the macro object be in flux. If you put a cat in a box, and place a dangerous radioactive isotope in it, then you essentially have three probable states once the radioactive isotope decays: the cat is dead; the cat is alive, or the cat is in a bizarre superposition of both dead and alive states. Yet when we open the box, the cat is either dead or alive, and can never be both simultaneously. Why is this so, and how did we resolve that strange paradox?

Much of the work that Wineland and Haroche have been doing centers on this very question. I don’t mean to say that they’ve solved the entire problem of what a quantum atomic particle is, or anything fundamentally philosophical* regarding the field of quantum physics, but I do know that their work has illuminated the stages by which an atom or photon resolves itself from a haze of probability into a classical particle, like a distant object comes into focus when we train a pair of binoculars onto it.

Their work is very different, yet very complementary. Here are quotes from Stockholm’s** press release package regarding the nature of Wineland’s research:

…electrically charged atoms or ions are kept inside a trap by surrounding them with electric fields. The particles are isolated from the heat and radiation in their environment by performing the experiments in vacuum at extremely low temperatures.

Actually those particles are created using a very interesting method outlined in the advanced background PDF from the Nobel website: they’re first energized by a laser, and then allowed to decay to a lower energy state — so low, in fact, that it’s close to absolute zero. Then, Wineland’s team further stimulates the atom with a laser so that it achieved something that’s halfway between two of the states that it could occupy. Left in a strange limbo between one state and another, the atom is now in a superposition of states, and its weird and wonderful properties can be studied.

In contrast, Haroche and his team created a cavity from extremely reflective superconducting glass, which contained a variable number of photons that bounced back and forth between the mirrors for an extremely long distance (a whopping 40,000 km, to be precise). To measure the presence of the photons, the team sends in very carefully prepared atoms that don’t absorb the photons but are changed by it; they undergo what’s known as a phase shift. As the press release package puts it,

…if you think of the atom’s quantum state as a wave, the peaks and the dips of the wave become shifted

Haroche’s team effectively built a nano-lab that could be used to chart the evolution of an atom as it went from a highly complex quantum state to one where it behaved essentially like a classical particle.

This could lead the way to those most magical of technologies that we’ve been dreaming about this century: a quantum computer.

*In fact, I’d be wholly unqualified to answer that.

** Only because I think saying “Stockholm” is so much cooler than saying “the Nobel committee”

The 2012 Nobel Prize in Physiology or Medicine

Yesterday, the Nobel committee in Stockholm announced that the 2012 Prize in Physiology or Medicine would be going to John B. Gurdon and Shinya Yamanaka for the discovery that adult, differentiated cells could be de-differentiated again into pluripotent cells.

In countries where research on embryonic stem cells is essentially frozen — like Japan, for instance — this variety of pluripotent cells could prove to be a boon. More importantly, experiments done by these men revolutionized our understanding of the cellular lifecycle; no longer was it unidirectional, where cells moved down a one-way path into specialization.

I especially liked SciAm’s profile of Yamanaka’s work. His research showed that a bare handful of genes — four, to be precise — could turn back cellular time and ‘regress’ the cell into its pluripotent state.

…[Yamanaka]uncovered 24 factors that, when added to ordinary mouse fibroblast cells and subjected to the correct culturing procedures, could create pluripotent cells virtually identical to stem cells. Yamanaka kept examining each factor and found that none could do the job alone; instead a combination of four particular genes did the trick.

Note the “virtually identical” in that paragraph.

Yamanaka and others do not think that iPS cells can replace their embryonic counterparts yet. “We don’t yet know if embryonic stem cells and iPS cells are truly equivalent,” says Konrad Hochedlinger of Massachusetts General Hospital’s Center for Regenerative Medicine.

There are other issues with pluripotent cells: they need to be injected with some kind of retrovirus, which would leave the new cells full of the potential to attack our immune system. They’ve been working on this, however, and now Yamanaka’s team has come up with a way to use a circular, double stranded round of DNA called plasmids to replace retroviruses.

Yamanaka’s lab reported success using plasmids, or circular pieces of DNA. Other retrovirus alternatives include proteins and lipid molecules.

The risks don’t end there. Since one of the genes that controls the induction of pluripotency is strongly cancerous, there’s a chance that the stem cells could become tumorous too. There’s still hope, though:

…the transcription factor c-Myc happens to be a powerful cancer gene, and the cells produced by Yamanaka’s team tended to become cancerous. “Making iPS cells is very similar to making cancer,” he explains. In principle, c-Myc may not be necessary: in mice, Yamanaka and a group led by Rudolf Jaenisch at the Massachusetts Institute of Technology found a way to avoid using c-Myc, in part, by optimizing culture conditions.