Rosbash, Hall, and Young Honored with Canada Gairdner International Award

Brandeis science faculty members Michael Rosbash and Jeff Hall were named today as 2012 recipients of the Canada Gairdner International Award, one of the world’s top prizes for biomedical research. Together with Michael Young (Rockefeller Univ.), they were honored “for pioneering discoveries concerning the biological clock responsible for circadian rhythms”. The trio has previously been honored with the 2011 Louis Gross Horwitz Prize and the 2009 Gruber Neuroscience Prize for this research.

The Gairdner Foundation in Toronto began giving awards in 1959 to recognize and reward the world’s most creative and accomplished biomedical scientists. So far about a quarter of the recipients have gone on to win a Nobel Prize. Also honored this year (for other work) were neuroscientist Tom Jessell and immunologist Jeffrey Ravetch.

Hall is now Professor Emeritus of Biology, and his influence is felt strongly in the strong Drosophila genetics community at Brandeis even though his lab is gone. The Rosbash lab continues to be a force for innovation in research on circadian regulation and mRNA processing. To hear more about Rosbash lab research, come to Wednesday seminar on April 4, when Michael will be the speaker. The title of his seminar is: 37 years at Brandeis (but who’s counting): Gene Expression and Circadian Rhythms.

Here’s some video the Gairdner Foundation posted on YouTube:

More information about this story at the following sites:

Gruber Foundation endows chair in Neuroscience

Brandeis Professor Michael Rosbash, was named last Thursday at faculty meeting as the inaugural Peter Gruber Endowed Chair in Neuroscience. The chair was established by the Peter and Patricia Gruber Foundation through a gift to Brandeis.

For more information, see the story at Brandeis NOW.

Horwitz Prize for Hall, Rosbash and Young

Columbia University will award the 2011 Louisa Gross Horwitz Prize to Jeffrey C. Hall, Michael Rosbash, and Michael W. Young “for their work on the molecular basis of circadian rhythms, the first demonstration of a molecular mechanism for behavior”. Hall is a Professor Emeritus of Biology at Brandeis, and Rosbash is an HHMI Investigator and Professor of Biology at Brandeis. The prize is awarded annually for outstanding basic research in biology or biochemistry. In the early 1980s, working at Brandeis, Hall and Rosbash combined their expertise in fly genetics and molecular biology to clone the Drosophila gene period, a key regulator of the circadian rhythm, as Young and his lab at The Rockefeller University did independently.

In subsequent years, research in the Hall and Rosbash labs at Brandeis led to transcriptional feedback models for the clock, discovery of additional genetic factors involved in the behavior, and discovery of neuroanatomical features involved in circadian rhythms. Circadian rhythms have been found in a very wide variety of organisms, and seem to be important in metabolism and disease.

Hall and Rosbash will receive their award in November at  a ceremony at Columbia University.

Is it the clock’s fault?

Brandeis researchers Jerome Menet and Professor Michael Rosbash (Biology Dept., Natl. Ctr. for Behavioral Genomics, and HHMI) review the relationships between psychiatric disease and the circadian clock in a review entitled “When brain clocks lose track of time: cause or consequence of neuropsychiatric disorders“. This review appeared recently in Current Opinion in Neurobiology. They discuss an increasing body of evidence that disorders in the clock may be directly involved in the etiology of these disorders.

Light buffers the wake‐promoting effect of dopamine

Sleep is driven and regulated by the integration of diverse internal and external (environmental) cues. Light is known to be a potent inhibitor of sleep in diurnal animals (awake during daylight hours and sleep at night), including both humans and fruit flies. Yet wakefulness does not scale linearly with light intensity and a lack of light does not automatically result in sleep. (Evolution seems unlikely to favor animals who become hyperactive in dangerously hot midday sunlight and fall asleep in an uncontrollable narcoleptic fashion when the sun goes down, unable to wake until the next morning.) The sleep regulatory system must be plastic — capable of weighing the relative importance of incoming sleep and wake‐promoting cues, and buffering the effects of those cues on sleep drive accordingly. In a recent Nature Neuroscience paper from a team led by postdoc Yuhua Shang (Rosbash lab), with collaborators from the Griffth, Pollack, and Hong labs at Brandeis, we determined at the cell and molecular level how the fruit fly, Drosophila melanogaster, is able to buffer the wake‐promoting effects of the neurotransmitters dopamine and octopamine in the presence of light in order to maintain a proper sleep:wake balance.

It is known that dopamine and octopamine both promote wakefulness in flies. Previous work in the Rosbash and Griffith labs has shown that 10 neurons in the Drosophila brain that release the neuropeptide pigment‐dispersing factor (PDF), known as the l‐LNvs, are critical for transducing the wake‐promoting effects of light. Quantifying mRNAs from all 18 PDF-expressing neurons revealed an enrichment of octopamine and dopamine receptors specifically in the ten wake‐promoting l‐LNvs. We wondered if the l‐LNvs were also able to respond to and transduce the wake‐promoting effects of dopamine and octopamine, and if so, how these effects were integrated with the wake‐promoting effects of light by these cells.

Figure: The l-LNvs use two parallel intracellular pathways to regulate the stimulating effects of DA and OA. Both DA and OA increase the cAMP levels in the l-LNvs. Light in the housing environment suppresses the effects of both DA and OA, but in different ways. In the case of dopamine, light induces increased expression of an inhibitory D2R receptor and in the case of octopamine, the effect is dependent on the circadian clock (Per.)

Using a fluorescence resonance energy transfer (FRET)‐based cyclic AMP reporter expressed in all 18 Pdf neurons, we were able to see robust responses to both octopamine and dopamine in only the t0 l‐LNvs, confirming the mRNA result. To verify that the l‐LNvs are in fact in close apposition to presynaptic octopaminergic and dopaminergic neurons, we looked for reconstitution of a split GFP protein between pre- and post‐synaptic cells. With different GFP fragments expressed at the membrane of the l‐LNvs and presynaptic dopaminergic or octopaminergic neurons, reconstituted GFP would only be visible if these cell populations were in close contact. Reconstituted GFP was seen in both cases around l‐LNv cell bodies and dendritic areas.

To determine the behavioral effect of increased dopaminergic neuron activity on sleep, we transiently hyper‐excited the dopaminergic neurons in flies using the Garrity lab’s heat‐activated dTrpA1 channel. When the housing temperature of flies expressing dTrpA1 in dopaminergic neurons was increased, activating dTrpA1 activity, flies exhibited increased wakefulness. Interestingly, this increased wakefulness was much greater in flies housed in constant darkness as compared to those housed in light:dark cycling conditions. This suggested that the l‐LNvs are a convergence point for the wakepromoting effects of dopamine and light. FRET analysis confirmed this, showing that the l‐LNv response to both dopamine and octopamine is much weaker in flies kept in light:dark conditions as compared to those kept in constant darkness. We then determined that light causes increased expression of an inhibitory dopamine receptor, resulting in a weaker excitatory response to dopamine by the l‐LNvs. In the case of octopamine, the circadian clock was found to regulate the effects of light. Such plasticity allows flies to maintain similar amounts of total sleep in varying environmental conditions, decreasing the relevance of internally generated wake‐promoting cues, in the presence of stronger environmental cues (light). It will be interesting to see how these results generalize to mammals, since light and dopamine also both promote wakefulness in mammals.

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/.

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