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.

Leslie Griffith Receives SASTRA-Obaid Siddiqi Award

SASTRA award


Model depicts how the integration of light, ambient temperature, the circadian clock and homeostatic sleep drive sets the balance between daytime and nighttime sleep [Parisky, K.M., Agosto Rivera, J.L., Donelson, N.C., Kotecha, S. and Griffith, L.C. (2016) “Reorganization of sleep by temperature in Drosophila requires light, the homeostat and the circadian clock” Curr Biol 26:882-892]

Leslie C. Griffith, Nancy Lurie Marks Professor of Neuroscience and Director of the Volen National Center for Complex Systems, has received the SASTRA–Obaid Siddiqi Award for excellence in life sciences. The prize is given by the Shanmugha Arts, Science, Technology & Research Academy (SASTRA) University in Thanjavur, India. Siddiqi was a pioneering molecular biologist and founder of the Molecular Biology Unit of the Tata Institute for Fundamental Research.

Griffith’s interests range from the biochemistry of neuronal signal transduction, in particular the role of CaMKII in memory formation, to the hierarchical relationships between complex behaviors such as sleep and learning. She has contributed to our understanding of these issues using genetic approaches in Drosophila melanogaster and believes that model systems have an important place in pioneering the understanding of basic biological processes. Her lab has been active in developing tools that allow interrogation of molecular and cellular processes with temporal and spatial resolution in freely behaving animals to bridge the molecule-behavior gap.

Griffith received the award on February 28, 2017.

Dynamics of GreB-RNA polymerase interaction

Larry Tetone, Larry Friedman, and Melissa Osborne, and collaborators from the Gelles lab (Brandeis University) and the Landick lab (University of Wisconsin-Madison) used multi-wavelength single-molecule fluorescence methods to for the first time directly observe the dynamic binding and dissociation of an accessory protein with an RNAP during active transcript elongation.

Their findings are detailed in the recent paper “Dynamics of GreB-RNA polymerase interaction.” (PNAS, published online 1/30/2017).

Read more at The Little Engine Shop blog

Research Funding For Undergrads: MRSEC Summer Materials Undergraduate Research Fellowships

The Division of Science wishes to announce that, in 2017, we will offer seven MRSEC Summer  Materials Undergraduate Research Fellowships (SMURF) for Brandeis students doing undergraduate research, sponsored by the Brandeis Materials Research Science and Engineering Center.

The fellowship winners will receive $5,000 stipends (housing support is not included) to engage in an intensive and rewarding research and development program that consists of full-time research in a MRSEC lab, weekly activities (~1-2 hours/week) organized by the MRSEC Director of Education, and participation in SciFest VII on Aug 3, 2017.

The due date for applications is February 27, 2017, at 6:00 PM EST.

To apply, the application form is online and part of the Unified Application: https://goo.gl/9LcSpG (Brandeis login required).


Eligibility

Students are eligible if they will be rising Brandeis sophomores, juniors, or seniors in Summer 2017 (classes of ’18, ’19, and ’20). No prior lab experience is required. A commitment from a Brandeis MRSEC member to serve as your mentor in Summer 2017 is required though. The MRSEC faculty list is: http://www.brandeis.edu/mrsec/people/index.html

Conflicting Commitments
SMURF recipients are expected to be available to do full time laboratory research between May 30 – August 4, 2017. During that period, SMURF students are not allowed to take summer courses, work another job or participate in extensive volunteer/shadowing experiences in which they commit to being out of the lab for a significant amount of time during the summer. Additionally, students should not be paid for doing lab research during this period from other funding sources.

Application Resources
Interested students should apply online (Brandeis login required). Questions that are not answered in the online FAQ may be addressed to Steven Karel <divsci at brandeis.edu>.

The Benefits of Middle Age

Almost all our cells harbor a sensory organelle called the primary cilium, homologous to the better known flagella found in protists. Some of these cilia can beat and allow the cell to move (eg. in sperm), or move fluid (eg. cerebrospinal fluid) around them. However, other specialized cilia such as those found in photoreceptor cells and in our olfactory neurons function solely as sensory organelles, providing the primary site for signal reception and transduction. The vast majority of our somatic cells display a short and simple rod-like cilium that plays crucial roles during development and in adulthood. For instance, during development, they are essential for transducing critical secreted developmental signals such as Sonic hedgehog that is required for the elaboration of cell types in almost every tissue (eg. in brain, bones, muscles, skin). In adults, cilia are required for normal functioning of our kidneys, and primary cilia in hypothalamic neurons have been shown to regulate hunger and satiety.

Given their importance, it is not surprising that defects in cilia structure and function lead to a whole host of diseases ranging from severe developmental disorders and embryonic lethality to hydrocephalus (fluid accumulation in the brain), infertility, obesity, blindness, and polycystic kidney among others. Often these diseases manifest early in development resulting in prenatal death or severe disability, but milder ciliary dysfunction leads to disease phenotypes later in life.

Much is now known about how cilia are formed and how they function during development. However, surprisingly, how aging affects cilia, and possibly the severity of cilia-related diseases, is not well studied. A new study by postdocs Astrid Cornils and Ashish Maurya, and graduate student Lauren Tereshko from Piali Sengupta’s laboratory, and collaborators at University College Dublin and University of Iowa, begins to address this question using the microscopic roundworm C. elegans (pictured below). These worms display cilia on a set of sensory neurons; these cilia are built by mechanisms that are similar to those in other animals including in humans. Worms have a life span of about 2-3 weeks, thereby making the study of how aging affects cilia function quite feasible.

benefits-midage

They find that cilia structure is somewhat altered in extreme old age in control animals. However, unexpectedly, when they looked at animals carrying mutations that lead to human ciliary diseases, the severely defective cilia seen in larvae and young adults displayed a partial but significant recovery during middle-age, a period associated with declining reproductive function. They went on to show that the heat-shock response and the ubiquitin-proteasome system, two major pathways required for alleviating protein misfolding stress in aging and neurodegenerative diseases, are essential for this age-dependent cilia recovery in mutant animals. This restoration of cilia function is transient; cilia structure becomes defective again in extreme old age. These results suggest that increased function of protein quality control mechanisms during middle age can transiently suppress the effects of some mutations in cilia genes, and raise the possibility that these findings may help guide the design of therapeutic strategies to target specific ciliary diseases. Some things can improve with aging!

Irving Epstein has been named AAAS Fellow

irving-epstein

In recognition of his contribution to the study of oscillating chemical reactions, Irving Epstein, the Henry F. Fischbach Professor of Chemistry, has been selected as a Fellow in the American Association for the Advancement of Science (AAAS).

Epstein, who in his 45 years at Brandeis has served as Provost and Dean of the Arts and Sciences, said he was honored to receive the award from the AAAS. “I’m delighted and grateful for the recognition,” he said. “It’s always nice to be appreciated by fellow scientists.”

 

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