Congratulations, Alex!

Congratulations to Alex Watson-Lazowski, who recently passed his PhD viva with minor corrections.

Alex was based in the Taylor Lab at the University of Southampton, where he applied Next Generation Sequencing to understand acclimation and adaption of Plantago lanceolata to a changing environment - and learnt a lot about the challenges of using RNA-Seq data without an available genome sequence!

Alex will be moving to Australia in July to take up a postdoctoral position in the Hawkesbury Institute for the Environment at the University of Western Sydney.

Research snapshot: June 2015

Research interests in the Edwards lab stem from a fascination with molecular basis of evolutionary change and how we can harness the genetic sequence patterns left behind to make useful predictions about contemporary biological systems.

The core research in the lab is the study of Short Linear Motifs (SLiMs), which are short regions of proteins that mediate interactions with other proteins. This research originated with Rich’s postdoctoral research, during which he developed a bioinformatics (sequence analysis) method for rational design of biologically active short peptides. He subsequently developed SLiMDisc, one of the first algorithms for successfully predicting novel SLiMs from sequence data - and coined the term “SLiM” into the bargain - before developing the first SLiM prediction algorithm able to estimate the statistical significance of motif predictions (SLiMFinder), which greatly increased the reliability of predictions. SLiMFinder has since spawned a number of motif discovery tools and webservers and is still arguably the most successful SLiM prediction tool on benchmarking data.

Current research is looking to develop these SLiM prediction tools further and apply them to important biological questions. Of particular interest is the molecular mimicry employed by viruses to interact with host proteins and the role of SLiMs in other diseases, such as cancer. Other work is concerned with the evolutionary dynamics of SLiMs within protein interaction networks.

Another area of research concerns the post-transcriptional regulation of protein expression. In collaboration with Dr Mark Coldwell (University of Southampton), we are asking the question: how does the ribosome choose where to start translating a protein? By combining bioinformatics screens with laboratory reporter assays, we are identifying proteins that are translated from non-canonical and/or multiple initiation codons. Possible roles of N-terminal variability in protein interactions and subcellular localisation are now under investigation.

Finally, the lab has a number of interdisciplinary collaborative projects applying bioinformatics tools and molecular evolution theory to experimental biology, often using large genomic, transcriptomic and/or proteomic datasets. These projects often involve the development of bespoke bioinformatics pipelines and a number of open source bioinformatics tools have been generated as a result.

New SLiMSuite release and GitHub site

A new download of SLiMSuite (release 2015-06-01) is now available. This is the first release in the new git repository at https://github.com/slimsuite/SLiMSuite. A tarball slimsuite.2015-06-01.tgz is also available, containing the same code. Once unpacked, it should be possible to pull down additional updates with git.

New EdwardsLab Homepage

The EdwardsLab has a new homepage:

http://www.slimsuite.unsw.edu.au

This blog will remain as the primary source of news and information but the new page gives a fresh landing page and some additional links to resources:

The old pages should now redirect but please point any out of date pages and/or link rot that you come across.

Honours and undergrad research opportunities (deadlines soon!)

There are several research opportunities for students in the Edwards Lab with deadlines coming up:

1. Mid-session Honours entry. Deadline: 4pm Friday 1^st of June. Please see the BABS website for more information.

2. BABS3301 Biomolecular Science Laboratory Project (Advanced) course. (See below.)

3. BABS Second-year student internships. Deadline: COB Friday 22/5/2015.

The lab has a number of projects available, of which three examples are listed below. I am happy to discuss other bioinformatics project options around the general theme of sequence analysis and/or protein-protein interactions. There are also some website/software engineering projects available.

Research focus

Applying biological sequence analysis and molecular evolution to study the molecular basis of protein-protein interactions.

Suitable for students who have majored in Biochemistry, Molecular Biology, Microbiology or Genetics. Projects are 100% computational; would suit students with computer programming experience and an interest in molecular evolution, or vice versa.

Example projects

Project 1: Molecular mimicry in host-pathogen interactions Many viruses hijack host cellular machinery through the molecular mimicry of host Short Linear Motifs (SLiMs). It is likely that pathogenic bacteria may employ similar strategies. This project will apply state-of-the-art SLiM prediction tools developed in our lab to published datasets of host-pathogen protein-protein interactions. This will help us understand how pathogens mess with their hosts – and how to stop them!

Project 2: Mining cancer genomics for disease mutations that disrupt protein function SLiMs tend to be involved in low affinity interactions and have a small number of amino acid residues that are required for function. These attributes make them potential sites of mutations that slightly disrupt cellular function, sometimes only in specific genetic backgrounds or environments. This project will combine methods for proteome-wide SLiM prediction with human genomics data and genetic variants associated with disease. This will focus on mutations in cancers, which affect many of the same pathways targeted by molecular mimicry in viruses.

Project 3: Yeast as a model for protein interaction dynamics In addition to giving us bread and beer, the yeast Saccharomyces cerevisiae is an awesome eukaryotic model organism. This project will compare proteinprotein interactions in humans and yeast to learn how both organisms exploit SLiMs and post-translational modifications to dynamically control the complex inner workings of their cells.

BABS3301 Biomolecular Science Laboratory Project

Students with a WAM of 75 or more who are enrolled in a Biochemistry, Genetics or Molecular Biology major in one of the BSc, BSc(Adv) or BMedSc programs should consider enrolling in the BABS3301 (Biomolecular Science Laboratory Project (Advanced) course. This course is designed to introduce you to research methodology, and to stimulate critical and lateral thinking in the context of problem solving. The course involves directed reading, laboratory work and use of internet resources. You will work on a research project under the supervision of a member of the academic staff. Enrolment in this course is by invitation and is based on academic performance and is restricted to Science and Advanced students enrolled in one of the BABS majors (i.e. Biotechnology, Genetics, Microbiology, Molecular Biology and Cellular Biology Major or Plans or the Biochemistry and Molecular Biology, Genetics or Microbiology and Immunology specialisations).

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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