Garrity lab finds moisture-sensing genes in mosquitoes

Summary figure for Garrity lab paperby Zachary Knecht, PhD candidate

As the solvent of living cells, water is critical for all life on earth.  This makes monitoring how environmental conditions impact evaporation and subsequently sensing and locating water sources important for animal survival. This is particularly critical for insects, whose small body size makes them highly susceptible to dehydration. In addition, moisture sensing, or hygrosensation, is also important for the spread of insect-born disease. Mosquitoes that spread malaria or viruses like dengue and Zika, not only need to locate bodies of standing water in which to lay eggs, but also home in on the moisture that emanates from our bodies when searching for a blood meal. This dual role for hygrosensing in mosquito biology makes their hygrosensory machinery a promising target for pest control strategies. Until now though, the genes and molecules that function in insect hygrosensation have been completely unknown.

In a pair of recent papers in the journal eLife, researchers in the Garrity Lab at Brandeis University, in collaboration with colleagues at the University of Lausanne in Switzerland, have uncovered the cellular and molecular mechanisms that underlie insect hygrosensation using the fruit fly Drosophila melanogaster. Like mosquitoes, fruit flies detect humidity through specialized, innervated hair-like structures located on their antennae called sensilla. Each hygrosensing sensilla contains one cell that responds to increasing humidity (a moist cell), and one that responds to decreasing humidity (a dry cell).  These papers demonstrate that the balance of activity between dry and moist cells allows the insect to seek out or avoid particular humidity levels, a preference which changes depending on how hydrated or dehydrated the fly is.

To identify the molecules involved in sensing moisture, the researchers looked for mutant flies unable to distinguish between humid and dry air. They found that animals with mutations in four different genes disrupted the behavior. Strikingly, each of these genes encoded a different member of the same family of sensory receptors, the so-called Ionotropic Receptors or IRs.  Although IRs are found only in invertebrates, they belong to the same family as the ionotropic Glutamate Receptors, which lie at the heart of communication between nerve cells in the animal brain, including the human brain.  IRs differ from these relatives in that instead of sensing signals sent by neurons, they detect signals coming from the environment.  IRs are best known to act as chemical receptors, but the group found that a subset of IRs act instead to sense humidity. The researchers found two broadly expressed IRs, Ir25a and Ir93a, were required by both the dry cells and moist cells while the other two IRs, Ir40a and Ir68a, were specifically required by the dry and the moist cells, respectively. This suggests that Ir25a and Ir93a contribute to the formation of both moist and dry receptors, while Ir40a and Ir68a provide the dry- and moist-specific subunits to the receptor. Consistent with this view, the loss of either Ir68a or Ir40a alone only partially reduces the animal’s ability to sense humidity, but animals with mutations in Ir25a, Ir93a or both Ir40a and Ir68a are completely blind to moisture.

Having identified the specific genes required for sensing moisture, the next step is to determine the precise mechanism by which humidity activates these receptors. Furthermore, these genes are conserved in mosquitoes and other disease vectors, providing a clear path to translate what’s known about fly hygrosensation into the mosquito. These papers lay the groundwork for new mosquito control strategies that aim to precisely inhibit their ability to seek out water to reproduce and to seek out hosts to bite and spread deadly pathogens.

SPROUT grant opportunity for 2015 announced

From the Brandeis Office of Technology Licensing:

The Brandeis Virtual Incubator invites members of the Brandeis Community (faculty, staff and students) to submit an application for the SPROUT Program. These Awards are intended to stimulate entrepreneurship on campus and help researchers launch their ideas and inventions from the lab to the marketplace.The SPROUT Program will provide pilot funding for innovative scientific projects within the Division of Science that require bench research, lab space, and/or lab equipment.

We will be awarding $50,000 to be shared among the most promising proposals.
Come get your questions answered at one of our upcoming information sessions.
Info Sessions: 
Thursday, February 26,  11:00 a.m.-12:00 p.m. (Volen, room 201)
Monday, March 2,  2:00 p.m.-3:00 p.m.   (Shapiro Science Center, 1st Floor Library, room 1-03)
Deadlines: Preliminary Proposals are due by Friday, March 6th
Please note, the introduction of the new SPARK Program geared towards innovative non-bench projects that have impact. An additional email will be sent detailing this program.
For more information on each program go to our website or contact the OTL program leaders,  Melissa Blackman for SPROUT and  Anu Ahuja  for SPARK.

Sleep and memory are connected by a pair of neurons in Drosophila

In a recent post on the Fly on the Wall blog, Neuroscience grad student Bethany Christmann talks about recently published research from Leslie Griffith’s lab:

 … [How are sleep and behavior] connected in the brain? Does sleep simply permit memory storage to take place, such that the part of the brain involved in memory just takes advantage of sleep whenever it can? Or are sleep and memory physically connected, and the same mechanism in the brain is involved in both? In a recent study published in eLife, researchers in the Griffith lab may have [uncovered the answer]. They found that a single pair of neurons, known as the DPM neurons, are actively involved in both sleep and memory storage in fruit flies.

Haynes PR, Christmann BL, Griffith LC. A single pair of neurons links sleep to memory consolidation in Drosophila melanogaster. eLife. 2015;4.

Mitosis: One Polo controls it all

On November 6, 2014, Cell Cycle published a paper from the Yoshida lab entitled “The budding yeast Polo-like kinase Cdc5 is released from the nucleus in anaphase for timely mitotic exit.” This study was authored by Vladimir V. Botchkarev Jr., Valentina Rossio, and Satoshi Yoshida.

The cell cycle is one of the most fundamental biological processes whose ultimate goal is cell division with equal content of DNA in both daughter cells. The process of cell division is regulated by many intracellular events which must occur in a sequential order. These events include mitotic entry, faithful chromosome segregation, mitotic exit, and cytokinesis. Over the past 25 years, the Polo-like kinase (Polo) has been established to play important regulatory roles in each of these processes. Although many mitotic substrates of Polo have been discovered, the mechanism by which Polo can coordinate all of these mitotic events has remained largely elusive.

To understand the mechanism by which Polo can target its many substrates in a sequential order during mitosis, we decided to study the budding yeast Polo kinase Cdc5, which has high conservation with the human Polo-like kinase 1.

We found that Cdc5-GFP dynamically changes its localization during the cell cycle: Cdc5 is found in the cytoplasm in S- through early G2-phase, it accumulates in the nucleus at metaphase, and is released again to the cytoplasm in anaphase. Blocking nuclear import of Cdc5 in metaphase leads to a prolonged metaphase duration, suggesting that nuclear Cdc5 is required for chromosome segregation. In contrast, blocking nuclear release of Cdc5 in anaphase results in a prolonged anaphase duration, a defect in activation of the cytoplasmic Mitotic Exit Network, and a defect in cytokinesis. This indicates that Cdc5 is released from the nucleus to the cytoplasm in anaphase for timely mitotic exit and cytokinesis. We further found that activation of the Cdc14 phosphatase, a known nuclear substrate of Cdc5, is required for Cdc5 nuclear release in anaphase.

Collectively, our work reveals that the budding yeast Polo-like kinase Cdc5 controls the timing of mitotic events by dynamically changing its sub-cellular localization. Furthermore, our data suggests the existence of a positive feedback look between Cdc5 and Cdc14 to regulate timely mitotic exit. Read more

Brandeis will host Gene Expression and RNA Seminar (GEARS) meeting this October

Gene Expression and RNA Seminars (GEARS) club is a monthly event that includes scientific talks on the Gene Expression, RNA and Chromatin. Every month it is held at a different institute in the Boston area.

Brandeis University will be hosting the October GEARS meeting on Thursday, October 30 in Rosenstiel 118 from 6:30 – 7.30 PM and will feature three talks from Boston area researchers.  After the talks, there will be a social hour. This event is free and all are welcome to attend.

Speakers List:

“Hijacking an editing enzyme to reveal the targets of RNA-binding proteins”
Aoife McMahon, PhD, Rosbash lab, Brandeis University

“Genome protection against transposons by the piRNA amplifier complex”
Jordi Xiol, PhD, Moazed lab, Harvard Medical School

“Linking cancer metabolism, DNA repair and epigenetics: SIRT6 provides some clues”
Raul Mostoslavsky, PhD, Associate Professor, MGH Cancer Center/Harvard Medical School/Broad Institute

GEARS Club is generously supported with the help of New England Biolabs and Cell Signaling Technology.
This event is also co-sponsored by the Brandeis Biology Office.

For more information please visit:
Twitter @gearsclub

Genetics Training Grant Retreat to be held Friday, 9/26/14

The annual Genetics Training Grant seminar is being held on Friday, September 26th at the Shapiro Campus Center Auditorium at Brandeis University. Four cutting-edge synthetic biologists: Timothy Lu, Ron Weiss, William Shih and Ahmad Khalil will share their research for the Synthetic Biology: Insights and Applications” symposium.
Brandeis graduate students and post-docs will have the opportunity to meet the speakers and present their work in a poster session after the talks. We encourage researchers from all departments to contribute. If you are currently, or previously were on the Genetics Training Grant, presentation of a poster is expected. 

Schedule for GTG Retreat

9:30-10:30 Ron Weiss (MIT, Dept. of Biological Engineering)
“Synthetic biology: from parts to modules to therapeutic systems.”
10:30-11:00 Coffee Break
11:00-12:00 Timothy Lu (MIT, Dept. of Biology Engineering)
“Synthetic biology for human health applications.”
12:00-1:30 Break/Lunch
1:30-2:30 William Shih (Wyss Institute)
“DNA nanostructures as building blocks for molecular biophysics and future therapeutics.”
2:30-3:30 Ahmad Khalil (Boston University, Biomedical Engineering)
“Building molecular assemblies to control the flow of biological information.”
3:30-5:00 Poster session
Shapiro Science Center 2nd floor.
All life sciences students are invited to present.

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