Metabotropic glutamate receptors: modulators of context-dependent feeding behaviour in C. elegans

Dillon J, Franks CJ, Murray C, Edwards RJ, Calahorro F, Ishihara T, Katsura I, Holden-Dye L, O’Connor V (in press). Metabotropic glutamate receptors: modulators of context-dependent feeding behaviour in C. elegans. J Biol Chem. Apr 13. pii: jbc.M114.606608.

Abstract

Glutamatergic neurotransmission is evolutionarily conserved across animal phyla. A major class of glutamate receptors are the metabotropic glutamate receptors (mGluRs). In C. elegans three mGluR genes mgl-1, mgl-2 and mgl-3 are organised into three sub-groups, similar to their mammalian counterparts. Cellular reporters identified expression of the mgls in the nervous system of C. elegans and overlapping expression in the pharyngeal microcircuit that controls pharyngeal muscle activity and feeding behaviour. The overlapping expression of mgls within this circuit allowed investigation of receptor signalling per se and in the context of receptor interactions within a neural network that regulates feeding. We utilized the pharmacological manipulation of neuronally regulated pumping of the pharyngeal muscle in wild type and mutants to investigate mgl function. This defined a net mgl-1 dependent inhibition of pharyngeal pumping which is modulated by mgl-3 excitation. Optogenetic activation of the pharyngeal glutamatergic inputs combined with electrophysiological recordings from the isolated pharyngeal preparations provided further evidence for a presynaptic mgl-1 dependent regulation of pharyngeal activity. Analysis of mgl-1, mgl-2 and mgl-3 mutant feeding behaviour in the intact organism after acute food removal identified a significant role for mgl-1 in the regulation of an adaptive feeding response. Our data describes the molecular and cellular organisation of mgl-1, mgl-2 and mgl-3. Pharmacological analysis identified that in these paradigms mgl-1 and mgl-3, but not mgl-2, can modulate the pharyngeal microcircuit. Behavioural analysis identified mgl-1 as a significant determinant of the glutamate-dependent modulation of feeding, further highlighting the significance of mGluRs in complex C. elegans behaviour.

PMID: 25869139

Åsa Pérez-Bercoff (Postdoctoral research associate)

Åsa Pérez-Bercoff has a background in molecular biology and bioinformatics, having completed an MSc in Molecular Biology (2003) and an MSc in Engineering (2006) in Sweden. She completed a PhD in the research group of Associate Professor Aoife McLysaght at the Genetics department, Trinity College Dublin. Her PhD research was on the function and evolution of human protein networks, using publicly available datasets for modelling and hypothesis testing, and included a brief collaborative visit to Associate Professor Gavin Conant at the University of Missouri.

Following her PhD, Åsa worked as a bioinformatician in the Cancer Proteomics Mass Spectrometry research group of Associate Professor Janne Lehtiö (Karolinska Institute) in Sweden before moving to Australia in 2012 to join the research research group of Associate Professor Gavin Huttley at the ANU, in collaboration with Professor Wieland Meyer, at the Westmead Millenium Institute and University of Sydney.

Åsa joined the Edwards Lab in 2015 and worked on viral motif mimicry for a while before switching to work on yeast genomics in collaboration with Microbiogen Pty Ltd.

EMPLOYMENT HISTORY

• 2012-2015: POSTDOCTORAL FELLOW , AUSTRALIAN NATIONAL UNIVERSITY, CANBERRA, ACT, AUSTRALIA.
• 2012: POSTDOCTORAL FELLOW, KAROLINSKA INSTITUTE, SOLNA, SWEDEN.

SUMMARY OF ACADEMIC QUALIFICATIONS

1. PHD – 2012 — UNIVERSITY OF DUBLIN, TRINITY COLLEGE, DUBLIN,IRELAND.
2. M.SC. IN ENGINEERING (SPECIALISING IN BIOINFORMATICS) – 2006 — CHALMERS UNIVERSITY OF TECHNOLOGY, GOTHENBURG, SWEDEN
3. M.SC. IN MOLECULAR BIOLOGY — 2003 — SÖDERTÖRNS HÖGSKOLA, FLEMINGSBERG, SWEDEN
4. CERTIFICATE IN INTERNATIONAL ENGLISH LANGUAGE TESTING SYSTEM (IELTS), GENERAL TRAINING, STOCKHOLM, SWEDEN, 2012
5. CERTIFICATES IN TECHNICAL DATA PROCESSING (BASIC AND INTERMEDIATE COURSES), FOLKUNIVERSITETET, BOARD OF EXTRAMURAL STUDIES AT STOCKHOLM UNIVERSITY, STOCKHOLM, SWEDEN, 2001
6. CERTIFICATE IN ADVANCED ENGLISH (CAE), UNIVERSITY OF CAMBRIDGE, LOCAL EXAMINATIONS SYNDICATE, STOCKHOLM, SWEDEN, 1999

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