Another way that flies sense temperature

If you remember your (bio-)physical chemistry, you’ll remember that most proteins are temperature sensitive. But which ones acts as the sensors that drive behavior in higher organisms? The Garrity Lab at Brandeis has been working on thermosensation in Drosophila, and previous work has implicated the channel protein TRPA1 as a key mediator of temperature preference and thermotaxis,  In a new paper in Nature, members of the Garrity lab working in collaboration with the Griffith and Theobald have have identified another protein, GR28B(D), a member of the family of gustatory receptor proteins, as another behaviorally important temperature sensor, involved in rapid avoidance of high temperatures. Authors on the paper include postdocs Lina Ni (lead author) and Peter Bronk, grad students April Lowell (Mol. Cell Biology) and Vincent Panzano (PhD ’13, Neuroscience), undergraduate Juliette Flam ’12, and technician Elaine Chang ’08.

  • Ni L, Bronk P, Chang EC, Lowell AM, Flam JO, Panzano VC, Theobald DL, Griffith LC, Garrity PA. A gustatory receptor paralogue controls rapid warmth avoidance in Drosophila. Nature. 2013.
  • story at BrandeisNOW

 

Turn up the heat, flies still eat

A mystery has been unfolding at the intersection of pungent chemicals, temperate temperatures, and a question of detection: how do insects discriminate the noxious from the innocuous?  At the center is a single protein, TRPA1; however, this puzzle has implications from human pain to bug spray.

The subject of this story, TRPA1, is an ion channel gaining notoriety as an arbiter of agony.  From mollusks to mammals, TRPA1 is a biological irritant detector: it responds to pungent chemicals like those in mustard, wasabi, and garlic.  As we chop our onions and the tears flow, behind the scenes is TRPA1, gated by the reactive chemicals that waft into the air.  In fact, TRPA1 may lurk below the surface for many forms of irritation – the burn, the itch, the cough – and is implicated in maladies ranging from asthma, to inflammation, and pain.

In insects the story takes a twist, as TRPA1 mediates two senses.  On the one hand, TRPA1 in fruit flies and mosquitoes responds to the same chemicals that act on vertebrate orthologs.  In this role, TRPA1 stimulates gustatory neurons of the fly, detecting pungent chemicals and suppressing feeding before it is too late.

On the other hand, insect TRPA1 also responds to warmth.  Led by Brandeis University’s Paul Garrityour lab demonstrated previously that TRPA1 is essential for the fruit fly Drosophila melanogaster to select a comfortable temperature (~25C, ~77F).  Furthermore, our lab has demonstrated that TRPA1 is directly gated by warming (above ~27C, ~80F) acting as a molecular temperature sensor.

This brings us to the mystery: if Drosophila TRPA1 is activated by nasty chemicals and prevents flies from eating, and also gets activated by heating, how can a fly eat in the heat?

In a recent article published in the journal Nature, our lab reveals the mechanism.  We identified two isoforms (from alternate promoters) of Drosophila TRPA1.  The known isoform is gated by both pungent chemicals and warming.  However, we identified a new isoform that is selectively gated by chemicals. Check out Figure 1: neurons expressing the first isoform respond to both chemicals and temperature whereas neurons expressing the new isoform respond selectively to chemicals.

We also found that the temperature-insensitive form was expressed in the gustatory system of the fly, while the temperature-sensitive isoform is expressed inside the brain, so is shielded from chemicals.  In this way, the fly can eat in the heat because only a temperature-insensitive TRPA1 is modulating feeding.

The importance of distinguishing these two senses became clear when we mis-expressed the temperature sensitive isoform in aversive gustatory neurons.  When these engineered flies were gently warmed, they began to vomit uncontrollably, a dramatic demonstration of the behavioral imperative to distinguish noxious from innocuous stimuli.  Check out this video to see for yourself.

We then examined TRPA1 isoforms from malaria mosquitoes and found the same functional dichotomy observed in Drosophila.  This may explain how mosquitoes use a single channel to hunt for warm-bodied prey and avoid noxious repellents, and may provide two new targets for pest control: push on the chemical isoform to get bugs to leave you alone, or pull on the warmth-sensor to lure them to their death!

Beyond bug-sprays and bug-zappers, we have some tantalizing clues to how TRPA1 may further modulate its own temperature- and chemical-sensitivity.  The exact mechanisms are not clear but may have implications for the function of human TRPA1.  So, the mystery continues, but one thing is certain: TRPA1 promises to keep things spicy.

Brandeis Profs are Pretty Fly

Last week the Genetics Society of America (or GSA) held their annual Drosophila Research Conference in sunny San Diego.  Following a 52 year tradition, the meeting brought together some of the world’s greatest scientific minds to discuss all things fruit fly (formally known as Drosophila melanogaster).  Brandeis Professor Leslie Griffith and alumnus Giovanni Bosco (PhD ’98), now at the University of Arizona, were among the meeting’s head organizers, and were visible figures throughout the course of the entire conference.

Brandeis was also a commanding presence throughout the keynote talks, with Biologist Michael Rosbash kicking off the first night’s festivities.  His lecture, which documented the history of fruit fly behavioral research, recounted a number of both professional and personal experiences with some of history’s most renowned Drosophila researchers, including Seymour Benzer and Brandeis’ own Jeff Hall.  Neuroscientist Paul Garrity further represented Brandeis with his keynote address, titled “From the Cambrian to the Sushi bar: TRPA1 and the Evolution of Thermal and Chemical Sensing”.   The talk, which discussed the molecular underpinnings of thermosensation in fruit flies, also demonstrated that these mechanisms are well conserved between many invertebrate and vertebrate species, and likely date back to a common ancestor that walked (crawled?) the earth millions of years before humans existed.  Other presentations encompassed a number of exciting topics, including aging, immunity, population genetics, evolution, and models of human disease.

Brandeis Professors Michael Rosbash (left) and Paul Garrity (right), both of whom were featured in this year’s Drosophila Research Conference Keynote Lectures.

 

The next meeting will be held on March 7-11, 2012 in Chicago, Illinois.  For more information, visit http://www.drosophila-conf.org/2012/.

Alex’s life as a fly barista

Alex Dainis ’11 writes about her experiences in the Garrity lab studying the genetics of nociception in fruit flies in her story “My life as a fly barista” on the Life@Deis blog.

Update: see the later story on this blog about the Nature paper on which Alex is an author.

Drosophila TRPA1 and the ancient origin of chemical nociception

Story today on Brandeis NOW about research from the Garrity lab:

Whenever you choke on acrid cigarette smoke, feel like you’re burning up from a mouthful of wasabi-laced sushi, or cry while cutting raw onions and garlic, your response is being triggered by a primordial chemical sensor conserved across some 500 million years of animal evolution, report Brandeis scientists in a study in Nature this week.

Kang et al., “Analysis of Drosophila TRPA1 reveals an ancient origin for human chemical nociception”

Rise and shine, little fly

Most animals sleep, but why they sleep and how the brain generates sleep is mysterious. In a recent study published in Neuron, postdoc Katherine Parisky and colleagues use genetic tools to manipulate the activity of neurons that control sleep in flies. Their results demonstrate that in the fly sleep is generated by GABAergic inhibition of a small cluster of peptidergic neurons within the circadian clock. Flies carrying mutations in this peptide, PDF, or its receptor, are hypersomnolent, similar to human narcoleptics who have defective signaling by the peptide hypocretin/orexin. These results suggest that the circuit architecture used to control arousal is ancient.

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