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

[LinkedIn]

QSLiMFinder: improved short linear motif prediction using specific query protein data

Palopoli N, Lythgow KT & Edwards RJ (2015). QSLiMFinder: improved short linear motif prediction using specific query protein data. Bioinformatics 31(14): 2284-2293. [PDF]

Abstract

Motivation: The sensitivity of de novo short linear motif (SLiM) prediction is limited by the number of patterns (the motif space) being assessed for enrichment. QSLiMFinder uses specific query protein information to restrict the motif space and thereby increase the sensitivity and specificity of predictions.

Results: QSLiMFinder was extensively benchmarked using known SLiM-containing proteins and simulated protein interaction datasets of real human proteins. Exploiting prior knowledge of a query protein likely to be involved in a SLiM-mediated interaction increased the proportion of true positives correctly returned and reduced the proportion of datasets returning a false positive prediction. The biggest improvement was seen if a short region of the query protein flanking the interaction site was known.

Availability and Implementation: All the tools and data used in this study, including QSLiMFinder and the SLiMBench benchmarking software, are freely available under a GNU license as part of SLiMSuite, at: http://bioware.soton.ac.uk.

Supplementary information: Supplementary data are available at the journal’s web site and at http://bioware.soton.ac.uk/research/qslimfinder/.

PMID: 25792551

Deadline for Semester 2 international PhD studentships

The UNSW deadline for Semester 2 PhD applications for International Students is 26 Feb 2015. To allow sufficient time for assessment and processing, any Edwards Lab applications must be received TODAY (23 Feb 2015) for Semester 2, 2015. (Supported applicants will still need to make a UNSW application for the deadline.) Any applications received after this date will be considered for Semester 1, 2016. Unfortunately, these things need to be planned and researched a long time in advance!

ABiC2014 posters on F1000Posters

Better late than never, both posters from ABiC2014 are now on F1000Posters, along with many other great posters from the conference:

Richard J Edwards, Ranjeeta Menon, Nicolas Palopoli & Jason FH Wong (2015) Molecular mimicry in viruses and cancer. F1000Posters 6: 101.

Nicolas Palopoli & Richard J Edwards (2014) Computational prediction of protein interaction motifs using interaction networks and 3-dimensional structures. F1000Posters 5: 1682.

Science News: Colorful corals protect the algae inside

Science News have picked up the recent Molecular Ecology paper, Fluorescent protein-mediated colour polymorphism in reef corals: Multi-copy genes extend the adaptation/acclimatization potential to variable light environments, including a lovely photo from corresponding author Prof Jörg Wiedenmann and Cecilia d’Angelo, who heads up the Coral Reef Laboratory at Southampton.

How to apply for a PhD in the Edwards Lab

Choosing the right lab and project in which to do a PhD is one of the most important decisions in the life of a scientist. It is in the best interests of all concerned to make sure that there is a good fit. To this end, there is now a lab PhD application form for all interested applicants. (Click the link or image to download.)

The purpose of the form is two-fold:

1. To assess the skills, experience, and interests of applicants.
2. To assess key CV points for those intending to apply for UNSW Scholarships.

The lab does not currently have any funding for students but I am happy to receive applications from funded students and students wishing to apply for UNSW scholarships or other schemes. Please check the UNSW key dates page for application deadlines etc. - students may want to delay their application and strengthen their experience/CV in the meantime.

Informal enquiries are welcome but generic “Dear Sir/Professor” emails will be ignored. Please read this blog post, “How (not) to apply for a PhD”, before applying.

Note: Applicants with insufficient bioinformatics experience will not be considered (see below). It is simply too much of a risk (for both student and supervisor) to take such a student on, as not everyone takes to purely computational work. You must also demonstrate good communication in English, which includes all email communication.

Available projects

There are no specific projects on offer and PhD research topics will ultimately be a collaborative decision based on the skills and interests of the student as well as the current status of various research in the lab. Available projects range from algorithm and bioinformatics resource development to primarily data analysis projects. Examples include, but are not limited to:

• Yeast genomics using long-read PacBio sequencing. We are particularly keen to get a student to work on aspects of our ARC Linkage grant, investigating the evolution of a novel biochemical pathway in yeast.
• De novo whole genome sequencing and assembly of the cane toad.
• The role of gene duplication in the evolution of snakes.
• The development of diploid genome assembly analysis tools.
• Development of network approaches to understanding SLiM-mediated protein-protein interactions. (Strong maths required.)
• Predictions of molecular mimicry from host-pathogen interaction data.
• Exploring the role of SLiM mutations in cancer and other human diseases.
• Development of a database of SLiM predictions.
• Benchmarking, optimising and extending SLiM discovery tools.

There is no single perfect applicant profile: please provide a frank and honest appraisal of your interests, skills and future goals in your application.

Submitting your application

Completed applications forms should be emailed with a CV and degree transcript to richard.edwards@unsw.edu.au. Please name each file with your family name, initials and document type, e.g.

EdwardsRJ.Application.docx
EdwardsRJ.CV.pdf
EdwardsRJ.Transcript.pdf

PDFs are preferred but MS Word *.docx files are also OK. Remember: attention to detail is very important in bioinformatics. Boxes in the application form may be resized but please keep answers succinct; you will be judged on the quality of your writing.

Note: Applicants will also need to submit a formal application through the UNSW Graduate Research School. This is not recommended until an agreement has been made to sponsor your application. Please also note that any agreement to sponsor your application is not agreement to take you on as a student. The final decision regarding supervision will not be made until after all of the applications have been received and processed by UNSW.

Masters and undergraduate project applicants

Applicants for undergraduate projects (Honours/SVRS) or Masters programs should use the same form but indicate the program that they are applying for.

Bioinformatics Experience Requirements

All projects are 100% computational. To be considered as an international PhD applicant, you must have completed at least one 100% computational project as part of your undergrad or masters, or have equivalent computational experience (e.g. work placement as a programmer or data analyst). Taught courses are not sufficient at this level unless you can also provide some evidence of skill at scripting/programming, such as an extensive body of work at Rosalind. Unfortunately, the risks are simply too high otherwise.