In Science, Yeast Smells You

Olfactory receptors represent one of the largest families of G-protein coupled receptors known. In the nose, smelly chemicals dissolve into mucosal layers and interact with the genetically "hyper-variable" regions of these receptors. Such interactions trigger molecular cascades that change the membrane potential of the olfactory cells. The chemical cocktail of a given smell triggers a characteristic response in the activity of olfactory neurons, and this sensory output is interpreted by our brains as the smelly world around us.

A significant portion of these hypervariable regions are "orphaned" in that we do not know what particular smelly chemicals can bind to them. It would be great to get these receptors out of the orphanage because we could use these them in a test tube to detect e.g. explosives. The problem is that mammalian cells, for a variety of reasons, are not as efficient in such screens as cells traditionally involved in screening e.g. bacteria and yeast.

Enter engineered brewers yeast. By hijacking a rat G-protein signaling network, and coupling it to a genetic reporter, Radhika et al engineered a rat's nose in a (probably not but nonetheless potentially) delicious malty culture tube. Instead of changing the membrane potential as in an olfactory receptor cell, the yeast cells grow green in UV light. And as a proof of principle they de-orphaned a rat receptor, showing that it preferentially bound DNT, a toxic chemical associated with explosives.

Does this adopted receptor work the same way in rat cells? They didn't test. Can the system be used in a high-throughput screen for other toxins? Not yet. That's probably why it wasn't published in Science. I guess the big deal is that this is the first complex mammalian signaling network to be re-constituted in the way-evolutionarily distant yeast. In fact I imagine it is this evolutionary distance that affords the system so much power, as a similar system reconstituted in a more phylogenetically related cell might lead to unwanted molecular "cross talk" that could interfere with normal cellular physiology. Such an orthogonal signaling system affords another handy use for the lowly organism that booze consumers have grown to love.

For a professional perspective on this system check out, http://www.nature.com/nchembio/journal/v3/n6/full/nchembio0607-306.html

Note from the future: the yeast used in this might have been baker's yeast, S. cerevisiae. Too lazy to look it up though.

Strange Effects of 7T

My very first MRI was in the 7 Tesla scanner here at the center, and I have to say it was a pretty scary experience. I've gotten used to it now, but the opening is very very small, and there are subjective effects of the high field - specifially I felt like I was curving around a bend when I was being put straight into the magnet. There's also some evidence for mild cognitive effects of the 7T field (see here) - I, for one, can attest to dizziness if I wave my head around in front of the magnet too much.

A decade-old study that I came across today finds evidence for another strange effect of the 7T field. Here is the entire abstract (click on title for link to PubMed):

1: Bioelectromagnetics. 1996;17(5):358-63. Links

Exposure to strong static magnetic field slows the growth of human cancer cells in vitro.

• Raylman RR,
• Clavo AC,
• Wahl RL.

University of Michigan Medical Center, Department of Internal Medicine, Ann Arbor, USA.

Proposals to enhance the amount of radiation dose delivered to small tumors with radioimmunotherapy by constraining emitted electrons with very strong homogeneous static magnetic fields has renewed interest in the cellular effects of prolonged exposures to such fields. Past investigations have not studied the effects on tumor cell growth of lengthy exposures to very high magnetic fields. Three malignant human cell lines, HTB 63 (melanoma), HTB 77 IP3 (ovarian carcinoma), and CCL 86 (lymphoma: Raji cells), were exposed to a 7 Tesla uniform static magnetic field for 64 hours. Following exposure, the number of viable cells in each group was determined. In addition, multicycle flow cytometry was performed on all cell lines, and pulsed-field electrophoresis was performed solely on Raji cells to investigate changes in cell cycle patterns and the possibility of DNA fragmentation induced by the magnetic field. A 64 h exposure to the magnetic field produced a reduction in viable cell number in each of the three cell lines. Reductions of 19.04 +/- 7.32%, 22.06 +/- 6.19%, and 40.68 +/- 8.31% were measured for the melanoma, ovarian carcinoma, and lymphoma cell lines, respectively, vs. control groups not exposed to the magnetic field. Multicycle flow cytometry revealed that the cell cycle was largely unaltered. Pulsed-field electrophoresis analysis revealed no increase in DNA breaks related to magnetic field exposure. In conclusion, prolonged exposure to a very strong magnetic field appeared to inhibit the growth of three human tumor cell lines in vitro. The mechanism underlying this effect has not, as yet, been identified, although alteration of cell growth cycle and gross fragmentation of DNA have been excluded as possible contributory factors. Future investigations of this phenomenon may have a significant impact on the future understanding and treatment of cancer.

Welcome New Contributors!

We have two new contributors to the blog, rendering the url a bit unfair, but we're not going to change it now! Keep an eye out for posts from Dark Hollow and AN, as well as the usual, always sporadic KD.

Nicotine enhances attention by turning off the default network

An article in today's Journal of Neuroscience elaborates on the effects of nicotine previously mentioned here .

The default network is a pattern of spontanious activation that occurs when the brain is at rest - some think of it as the 'daydreaming' or 'zoning out' network. When the brain is engaged in a cognitive task (memory recall, problem solving, shifting attention, etc) the default network is inhibited. When the brain is "just sitting there" (staring at the wall, waiting in line at the bank) the default network fires up.

Here's a picture of it:



(Picture courtesy Justin Vincent.)

In smokers, a nicotine patch switched off scattered parts of the default network and also improved reaction time in an attention task.

Mice made to see a rainbow of colours

Gerald Jacobs at UCSB has introduced one genetic mutation into mice and enabled them to see a wider range of colors. Although the mutation only affected the photoreceptors in the retina, the mouse's cortical circuitry updated to account for the extra photoreceptors and can translate the output into colors.

The implications for humans are pretty cool - night vision without goggles, electromagnetic vision, or bee-like ultraviolet vision could be only one small genetic mutation away.

For more, check out the summary over at nature.com (no login required).

(picture from nature.com)

Neuroscience Lectures

The NIH has over 100 Neuroscience talks available for everyone to watch for free online (Realplayer) or as downloadable Podcasts. I've only scratched the surface of these so far, having watched Bob Wurtz's attention talk and Roger Tootell's ventral stream fMRI talk. The archives are searchable by topic or by author and they are still adding new talks as they happen. They have a whole archive of talks on subjects other than neuroscience as well.

NIH neuroscience talks.

Announcing new mini-blog

I've been really busy with work but hopefully will find time to write a few more posts in the near future. I know you're all (all two of you) on the edge of your seats waiting for more summaries of cutting edge research and pictures of retinotopic activiation.

In the meantime, however, you can check out my shiny (and low maintenance) new tumbalog. It's at:

kdevaney.tumblr.com

Papers

This is an in-development piece of software (only for Macs) to manage a digital collection of articles. It's called Papers, and it bears a striking similarity to iTunes, which I think will be an advantage, since many people are already familiar with the user interface. It looks like it will automatically retreive author, title and journal info from PubMed, which is a great help to me - I have tons of articles on my computer named something like sd-article178465749.pdf. I rely heavily on Spotlight to find articles on my computer, but after this comes out, maybe I won't have to.

**UPDATE** - Papers is now in its third public preview stage, and ArsTechnica has written a very comprehensive review.

How to do Research at the MIT AI Lab

While this guide contains a bit of outdated information,

(from the section on giving a talk: If you must point at the overhead, don't actually touch the transparency since you will make it jerk around.)

there's also a lot of useful content about research and networking

(from the 'Getting Connected' section: When a paper cites something that looks interesting, make a note of it. Keep a log of interesting references. Go to the library every once in a while and look the lot of them up. You can intensively work backward through a ``reference graph'' of citations when you are hot on the trail of an interesting topic.)

Retinotopy

(from Hadjikhani et al, Nature Neuroscience, 1998)