Summers, Philip et al. (2015) International Worm Meeting "Modulation of glutamatergic signaling in C. elegans."

Komuniecki, Richard, Summers, Philip, Ortega, Amanda, Bamber, Bruce

[International Worm Meeting, 2015]

The glutamatergic ASH sensory neurons are essential for the initiation of aversive responses to dilute 1-octanol. To identify and localize the glutamate receptors involved, we screened animals with null alleles for each of the previously identified or predicted glutamate-gated cation and anion channel subunits. Not surprisingly, given the array of ASH downstream synaptic partners, a number of the glutamate receptor mutants yielded phenotypes in various aspects of the modulated ASH mediated aversive responses. For example, the initiation of aversive responses in animals with null alleles for either avr-14 or glc-4, predicted to encode glutamate-gated Cl- channel subunits, was not stimulated by food or 5-HT, compared to wild type animals. In contrast, animals overexpressing either avr-14 or glc-4 initiated aversive response more rapidly than wild type animals off food. AVR-14 has been characterized extensively and encodes a homomeric glutamate-gated Cl- channel. In contrast, GLC-4 is the most distantly related of the predicted glutamate-gated Cl- channel subunits and has not been characterized. Therefore, GLC-4 was expressed heterologously in Xenopus oocytes to determine ligand-specificity and over the 100 ligands were examined. None activated a Cl- current in the oocytes. In contrast, GLC-4 expression with AVR-14 or AVR-15, well characterized glutamate-gated Cl- channel subunits, reduced peak Cl- currents and glutamate affinity, suggesting the GLC-4 interacted with these subunit to alter channel properties. This result appeared to be specific for glutamate-gated Cl- channels, as GLC-4 co-expression with MOD-1 that forms a 5-HT dependent Cl- channel had no effect on MOD-1 signaling. These studies are continuing to localize AVR-14 and GLC-4 in the ASH-mediated locomotory circuit at both the cellular and subcellular levels to determine their roles in ASH signaling and, more importantly, to determine if they associate in vivo.

Summers, Philip et al. (2013) International Worm Meeting "Sensory inputs are centrally integrated to modulate nociception in Caenorhabditis elegans."

Komuniecki, Richard, Ortega, Amanda, Summers, Philip

[International Worm Meeting, 2013]

In C. elegans, sensory neurons synapse onto a layer of interneurons that, in turn, synapse onto the command interneurons to modulate sensory-mediated locomotory decision-making. This study is focused on understanding how multiple sensory inputs are integrated by the AIB interneurons to modulate aversive responses to dilute octanol mediated by the ASH sensory neurons. Ablation of the AIBs decreased the rate of spontaneous reversal, but, in contrast, decreased the time taken to initiate reversal in responses to dilute octanol. In fact, inhibition of AIB signaling using a variety of approaches also decreased the time taken to initiate an aversive responses. The ASH, ADL, ASE, and AWC sensory neurons provide the major glutamatergic inputs into the AIBs, so to examine the role of glutamatergic signaling from these neurons on ASH-mediated behaviors, eat-4 that encodes a vesicular glutamate transporter was selectively overexpressed on the assumption that eat-4 overexpression would increase tonic glutamatergic signaling. Selective eat-4 overexpression in the ASHs, ADLs or ASEs decreased the time taken to initiate reversal off food, while eat-4 overexpression in the AWCs abolished the 5-HT stimulation of aversive responses. To identify the glutamate receptors involved, eat-4 was selectively overexpressed in animals with null alleles for glutamate-gated anion and cation channels and once the appropriate receptors were identified, their specific roles in the AIBs were confirmed by AIB-specific knockdown. As predicted, ASE signaling inhibited the AIBs by activating the glutamate-gated Cl- channel encoded by avr-14 and AWC signaling inhibited the 5-HT stimulation of aversive responses by activating the AMPA-like glutamate gated channel, GLR-1. Indeed, the AIB-specific overexpression of avr-14 decreased the time taken to initiate reversal off food and the AIB-selective overexpression of glr-1 abolished food or 5-HT stimulation. These studies are continuing to examine how multiple sensory inputs are integrated in the modulation of both spontaneous and sensory-evoked reversals and may provide useful insights into disorders associated with the altered sensory integration. Supported by NIH grant AI-145147.

Broverman SA et al. (1992) Worm Breeder's Gazette "Transformation Rescue of him-8"

Meneely PM, Broverman SA

[Worm Breeder's Gazette, 1992]

1) him-8, him-5 and him-1 asymmetrically affect recombination (pairing?) of the X chromosome. - 2) Transformation rescue of him-8. Sherryl Broverman and Philip Meneely, FHCRC, 1124 Columbia St., Seattle WA 98104, (206) 667-4523i FAX 206 667 4737

Harris, Gareth P. et al. (2009) International Worm Meeting "Neuropeptides are essential for the serotonergic stimulation of aversive responses mediated by the ASH sensory neurons."

Summers, Philip, Hapiak, Vera, Komuniecki, Richard, Wragg, Rachel, Korchnak, Amanda, Harris, Gareth P.

[International Worm Meeting, 2009]

Serotonin modulates many key behaviors in C. elegans, including the stimulation of aversive responses to dilute octanol mediated by the ASH sensory neurons (Harris et al., 2009, J. Neuroscience 29, 1446-1456). The serotonergic stimulation of ASH-mediated aversive responses requires the expression of SER-5 in the ASHs, but the site of SER-5 action is unclear. For example, SER-5 signaling may increase the release of glutamate and/or neuropeptides from the the ASHs. Indeed, the ASHs express multiple peptide encoding genes, including nlp-3 and nlp-15, and the peptides encoded by these genes have multiple effects on ASH signaling. For example, nlp-3 null animals exhibit wild-type basal responses to dilute octanol, but do not increase aversive responses in the presence of food or 5-HT. In contrast, nlp-15 null animals exhibit elevated basal responses to dilute octanol in the absence of either food or 5-HT and these elevated basal responses are not inhibited by octopamine. As predicted, animals overexpressing nlp-15 respond only weakly to dilute octanol and exhibit dramatically reduced basal responses. Interestingly, in these nlp-15 overexpressors, aversive responses can be stimulated to near wild-type levels by food or 5-HT. Together, these results suggest that nlp-15 inhibits ASH signaling by a mechanism that may not directly involve NT release from the ASHs. These observations have been confirmed by the ASH rescue and RNAi knockdown of nlp-15 and nlp-3. In addition, we have identified a number of other genes encoding peptides and peptide receptors that are also involved in modulating various aspects of ASH mediated signaling, highlighting the complexity of peptidergic modulation. These studies are continuing with the goal of identifying the receptors and downstream signaling pathways mediating the differential effects of nlp-3 and nlp-15 on signaling in the ASH sensory neurons.

Starr, D. et al. (2015) International Worm Meeting "UC Davis-University of Maryland Eastern Shore Graduate Admissions Pathway: Collaborating to broaden participation in molecular and cellular biology."

Starr, D., Hom, C.

[International Worm Meeting, 2015]

STEM professionals in the 21st century remain predominantly Caucasian/white, in spite of decades of work by professional societies, colleges and universities, and individual scientists to broaden participation. This multifaceted problem includes concerns among students and faculty at minority-serving institutions about the economics of career choice, family pressure to pursue a career in a biomedical field, and limited exposure to natural history. Further, institutional efforts in recruitment by research universities remain rooted in graduate fairs that target senior undergraduates from groups underrepresented in science, whereas connections made via shared research networks provide a more sure means to admission in molecular and cell biology. The UC Davis-University of Maryland Eastern Shore (UMES) Molecular and Cellular Biology Graduate Admissions Pathways (MCBGAP) program addresses this challenge via collaborations between faculty at the two institutions and a research co-mentoring program that brings UMES undergraduates to UC Davis for summer research. The program is funded by a grant from the University of California Office of the President and the UC Davis College of Biological Sciences.MCBGAP supported two cohorts of five UMES students in the summers of 2014 and 2015. The MCBGAP program consists of reciprocal student-faculty visits, close interactions between key UC Davis and UMES faculty, monthly Skype meetings that involve mentors and students, and research, professional development, and field trips in the summer. MCBGAP has catalyzed change both at UMES, where students are given the opportunity to self-identify as researchers at a tier 1 research university, and at UC Davis, where increased numbers of faculty recognize the need to be proactive in graduate recruiting and admissions, and multiple deans have committed time to mentor students and funds to support additional undergraduates from Historically Black Colleges and Universities for summer research and mentoring. The experience has also inspired us to apply for a Postbaccalaureate Research Education Program (PREP) from the NIH.

Gary Williams et al. (2006) European Worm Meeting "Curating Wormbase Gene Structures"

Tamberlyn Bieri, Darin Blasiar, John Spieth, Anthony Rogers, Gary Williams, Philip Ozersky, Paul Davis

[European Worm Meeting, 2006]

Gary Williams1, Paul Davis1, Anthony Rogers1, Philip Ozersky2, John Spieth2, Tamberlyn Bieri2, Darin Blasiar2. WormBase is an international consortium of biologists and computer scientists from Caltech (USA), Cold Spring Harbor Laboratory (USA), Wellcome Trust Sanger Institute (UK) and the Genome Sequencing Center at Washington University (USA).. WormBase is dedicated to providing the research community with accurate, current, accessible information concerning the genetics, genomics and biology of C. elegans, and some related nematodes. WormBase can be freely accessed at www.wormbase.org, and is also available for download at ftp://ftp.wormbase.org/pub/wormbase A new data release is produced every three weeks. Recently some new datasets have been added to the database to aid curation.The protein products from automated gene prediction in C. remanei have been mapped to the C. elegans genome; InterPro motifs are no longer taken from SwissProt annotations, but are directly predicted from the C. elegans proteins; contigs of ESTs from other nematode species produced by the NEMBASE and Nematode.net projects have been mapped to the genome and a new set of TEC-REDs have been mapped to the genome resulting in 3,325 new trans-spliced sites which mark the 5'' ends of genes or isoforms. Work is underway to classify and curate transposons and we intend to add Mass-Spec data from several sources to improve coding sequence validation.. Over the last year the curated coding sequences have increased from 19,854 to 20,060 and alternately spliced isoforms have increased from 2,772 to 2,883. The number of genes where every base of every exon is confirmed by EST evidence has increased from 6,427 to 6,584. In the C. elegans proteins there have been 630 modified entries, 440 deleted entries, 709 new entries and 64 reappeared entries.. WormBase is supported by a grant from the National Human Genome Research Institute at the US National Institute of Health #P41 HG02223 and the British Medical Research Council.