Friday, 23 September 2016

Predicting Motif Mimicry in Viruses

Sobia will be presenting the initial work from her PhD project today at the EMBO Workshop, The modularity of signalling proteins and networks at Seefeld in Tirol, Austria. Her talk is on:

Predicting Motif Mimicry in Viruses

Viruses mimic host motifs to hijack the host cellular machinery. Their interaction with host protein domains is through Short Linear Motifs (SLiMs). SLiMs are short stretches of amino acids (~3-10) which are involved in post translational modifications (PTMs), protein-protein Interactions (PPIs), cell regulation and cell compartment targeting. To date, several studies have been conducted to identify PPIs, but no specific study to see how well different PPI capturing methods capture SLiMs-mediated interactions. The main objectives of this study are 1) to predict Domain Motif Interactions (DMIs) among viral and host proteins 2) to find whether virhostome (virus-human interaction) data is enriched for DMIs and, 3) to see which PPI method is better for studying DMIs. Results have shown that virhostome data is enriched for DMIs and can be a good source to study motif mimicry in viruses. The permutation test showed more enrichment for TAP data as compared to the Y2H data. Moreover, novel candidate DMIs have been discovered which need further validations. The outcome of this study will be helpful in uncovering unique strategies of viruses to interact with human proteins which will eventually be significant for pathogen research.

Poster to follow.

Thursday, 25 August 2016

Honours and undergrad research opportunities

Honours

BABS are currently recruiting the next cohort of Honours students for Semester 1 2017. As usual, the EdwardsLab is looking to recruit enthusiastic students in two main areas:

1. Functional genomics using long-read PacBio sequencing. We are particularly keen to get a student to work on either (a) aspects of our ARC Linkage grant, investigating the evolution of a novel biochemical pathway in yeast, or (b) de novo whole genome sequencing of the cane toad. We also have a number of projects with bacteria for those with a keen interest in microbiology. In each case, the lab is collaborating with experts in the relevant organisms.

2. Applying biological sequence analysis and molecular evolution to study the molecular basis of protein-protein interactions. The main lab software, SLiMSuite has a number of improvements and developments that would benefit from some dedicated attention from a research student. We are also looking for someone who might want to help develop the lab servers.

More details of honours can be found on the BABS website, or please get in touch if you have questions about specific projects. Applications from non-UNSW students are also encouraged.

* BABS are also running an Honours information and networking night on 16th September.*

Summer Vacation Research Scholarships

BABS is once again running its highly successful Summer Vacation Research Scholarship (SVRS) scheme and the EdwardsLab are looking to take on one or two students in the same areas as indicated above.

How to apply

We do not yet have a specific undergraduate application form but it is helpful if you can follow the PhD application process and just make it clear that you are interested in Honours or SVRS. As well as helping select between applicants, this form is also useful for me to make sure that students are assigned an appropriate project.

Friday, 19 August 2016

Plant adaptation or acclimation to rising CO2? Insight from first multigenerational RNA-Seq transcriptome

Watson-Lazowski A, Lin Y, Miglietta F, Edwards RJ, Chapman MA & Taylor G (2016): Plant adaptation or acclimation to rising CO2? Insight from first multigenerational RNA-Seq transcriptome. Glob Chang Biol. Adv. access. doi: 10.1111/gcb.13322

Abstract

Atmospheric carbon dioxide (CO2 ) directly determines the rate of plant photosynthesis and indirectly effects plant productivity and fitness and may therefore act as a selective pressure driving evolution, but evidence to support this contention is sparse. Using Plantago lanceolata L. seed collected from a naturally high CO2 spring and adjacent ambient CO2 control site, we investigated multigenerational response to future, elevated atmospheric CO2 . Plants were grown in either ambient or elevated CO2 (700 μmol mol-1 ), enabling for the first time, characterization of the functional and population genomics of plant acclimation and adaptation to elevated CO2 . This revealed that spring and control plants differed significantly in phenotypic plasticity for traits underpinning fitness including above-ground biomass, leaf size, epidermal cell size and number and stomatal density and index. Gene expression responses to elevated CO2 (acclimation) were modest [33-131 genes differentially expressed (DE)], whilst those between control and spring plants (adaptation) were considerably larger (689-853 DE genes). In contrast, population genomic analysis showed that genetic differentiation between spring and control plants was close to zero, with no fixed differences, suggesting that plants are adapted to their native CO2 environment at the level of gene expression. An unusual phenotype of increased stomatal index in spring but not control plants in elevated CO2 correlated with altered expression of stomatal patterning genes between spring and control plants for three loci (YODA, CDKB1;1 and SCRM2) and between ambient and elevated CO2 for four loci (ER, YODA, MYB88 and BCA1). We propose that the two positive regulators of stomatal number (SCRM2) and CDKB1;1 when upregulated act as key controllers of stomatal adaptation to elevated CO2 . Combined with significant transcriptome reprogramming of photosynthetic and dark respiration and enhanced growth in spring plants, we have identified the potential basis of plant adaptation to high CO2 likely to occur over coming decades.

PMID: 27539677

Wednesday, 6 July 2016

SMBE2016: Investigating the evolution of new biochemical pathways in baker’s yeast Saccharomyces cerevisiae

Well done to Åsa for her oral presentation at SMBE2016 (#204):

Investigating the evolution of new biochemical pathways in baker’s yeast Saccharomyces cerevisiae

Åsa Pérez-Bercoff, Tonia L. Russell, Philip J. L. Bell, Paul V. Attfield & Richard J. Edwards

Abstract

Understanding how new biochemical pathways evolve in a sexually reproducing population is a complex and largely unanswered question. We have successfully evolved a novel biochemical pathway in yeast using a sex based population approach.

For over 30 years, wild type Saccharomyces has been widely reported to not grow on xylose at all, but we discovered that most strains can grow, albeit at almost undetectable rates. A mass mated starting population of Saccharomyces cerevisiae strains was evolved under selection on Xylose Minimal Media (XMM) with forced sexual mating every ~two months for 1463 days. This produced a population that could grow on xylose as a sole carbon source. Initial studies show the xylose growth trait is quantitative and presumably governed by many genes. To investigate the evolution of the xylose phenotype, a xylose utilising strain MBG11a was isolated. MBG11a was sequenced with PacBio RSII long read sequencing at the Ramaciotti Centre for Genomics. A high quality complete genome was assembled de novo using the hierarchical genome-assembly process (HGAP3) using only PacBio non-hybrid long-read SMRT sequencing data, corrected using Quiver, and compared to the genome of the S. cerevisiae S288C reference genome.

Approximately 98.5% of the MBG11a genome could be aligned to S288C at 99.5% sequence identity, with over 15,000 non-synonymous and 200 nonsense SNP differences. We have crossed MBG11a with a reference wild type yeast strain (X2180 gal2, Xyl-) and are testing offspring on different minimal media in an attempt to identify MBG11a variants responsible for the novel growth phenotype.

Understanding what has occurred in the evolving yeast population, and how the yeast genome adapted under the selection pressures is of broad interest as it allows experimental analysis of how novel complex biological functions can evolve in an organism.

Monday, 20 June 2016

Transcriptome analysis of human brain tissue identifies reduced expression of complement complex C1Q Genes in Rett syndrome

Lin P, Nicholls L, Assareh H, Fang Z, Amos TG, Edwards RJ, Assareh AA, Voineagu I (2016): Transcriptome analysis of human brain tissue identifies reduced expression of complement complex C1Q Genes in Rett syndrome. BMC Genomics 17(1):427. doi: 10.1186/s12864-016-2746-7.

Abstract

BACKGROUND: MECP2, the gene mutated in the majority of Rett syndrome cases, is a transcriptional regulator that can activate or repress transcription. Although the transcription regulatory function of MECP2 has been known for over a decade, it remains unclear how transcriptional dysregulation leads to the neurodevelopmental disorder. Notably, little convergence was previously observed between the genes abnormally expressed in the brain of Rett syndrome mouse models and those identified in human studies.

METHODS: Here we carried out a comprehensive transcriptome analysis of human brain tissue from Rett syndrome brain using both RNA-seq and microarrays.

RESULTS: We identified over two hundred differentially expressed genes, and identified the complement C1Q complex genes (C1QA, C1QB and C1QC) as a point of convergence between gene expression changes in human and mouse Rett syndrome brain.

CONCLUSIONS: The results of our study support a role for alterations in the expression level of C1Q complex genes in RTT pathogenesis.

PMID: 27267200

Thursday, 26 May 2016

Honours applications close next Friday (3 June)

We still have space in the group for one more Honours student, with a variety of projects available to work on PacBio SMRT data for bacteria, yeast or cane toad de novo genome assembly. Please get in touch if you are interested. (Better still, fill in the lab application form, making it clear it’s for Honours, not PhD!) The deadline is Friday, 3rd of June. See the BABS website for more details.