Tag Archives: pathogens

Job: Northern Arizona University – Pathogen and Microbiome Institute

(Even though this already had a closing in Dec, there is still interest in more applications to this position).

One tenure track assistant professor faculty position will be filled in the Pathogen and Microbiome Institute, with tenure assignment to an academic department relevant to the faculty member’s expertise (e.g., Department of Biological Sciences, School of Informatics and Computer Science and Cyber Systems) beginning August 21, 2017.

Job Description

Individuals are invited to apply for an assistant professor faculty position in the Pathogen and Microbiome Institute at Northern Arizona University. We are seeking individuals with research interests that complement existing strengths in basic or translational pathogen and microbiome research, which may include bioinformatics, genomics, immunology, molecular epidemiology, microbiology, population genetics, disease ecology, phylogeography, clinical and environmental microbiology expertise. This is a research intensive position with competitive teaching loads in subject areas that will be dictated by the applicant’s expertise. Evidence of grant potential will be required.

The successful candidates will be expected to: (1) develop and/or transfer an intensive research program that is supported by awards from extramural agencies; (2) contribute to the university graduate training program with M.S. and Ph.D. students, and postdoctoral fellows; and (3) perform service for the department, university, and profession.

A word about databases

Logo for fungal GenomesReport concludes that a fungal genome database is of “the highest priority”.

This is the title as listed in PubMed for this article from Future Medicine about the AAM report on charting future needs and avenues of research on the fungal kingdom.

The need for a comprehensive database for information about fungi, starting at least with systematic collections of genomic and transcript data, is highlighted as a major need.  Really and sort of new database effort should strive to be more comprehensive and include genetic and population data (alleles, strains) and information like protein-protein, protein-nucleic acid interactions (as Pedro mentioned). But on top of that it, it needs to be comparative so that information from systems that serve as great models can be transferred to other fungal systems that are being studied for their role as pathogens or interacting in the environmental.

Affordable next-gen sequencing will allow us to obtain genome and transcript sequence for basically all species or strains of interest.  Researchers with no bioinformatics support in their lab will likely be able to outsource this to a company or campus core facility.  But how can they easily map in the collective information about genes, proteins, and pathways onto this new data?  And have it be a dynamic system that can update as new information is published and curated in other systems.

I think this has to be the future beyond setting up a SGD, CGD, etc for every system.  The individual databases are useful for a large enough community where there are curators (and funding), but we will have to move to a more modular system in the future (aspects of which are in GMOD) that can have both an individual focus on a specific species/clade and a more comprehensive view of the that is comparable across the kingdom.  There are 100+ fungal genomes, but the community size for some of them are in the dozens of labs or less. How can they take advantage of the new resources without an existing infrastructure of curators?  Their systems serve an important need in a research aim, but how can discoveries there make its way back into the datastream of othe systems?

I see it as there are several ways one would interact with a system that provided single-genome tools as well as a framework for comparative information.  At a gene level, one might be looking for all information about a specific gene, based on sequence similarity searches, or starting with a cloned gene in one species. Something akin to Phylofacts or precomputed Orthogroups for defining a Gene but with more linking information about function by linking in information from all sources.  So a comparative resource, but also tapping into curated andliterature mined data.

At a genome level, one might want to do whole genome comparisons of gene content from evolutionarily defined families genes (gene family size change) or at a functional level.  To start out with, each gene/protein would already need a systematic functional mapping.  This could be as simple as running InterProScan on every protein, expanded to find Orthogroups (or OrthoMCL orthologs) and transfer function from model systems, and finally even more advanced, do further classified better with tools like SIFTER.

Interlinked with these orthologous and paralogous gene sets would be anchors for analyses of chromosomal synteny and even comparative assembly including tools like Mercator.  Certainly things like all of this exist but making it more pluggable for different sets of species would be an important additional component.

At a utility level, the gene annotation and functional mapping of all this information should be possible. I would imagine a researcher could upload the sequence assembly they received from the core facility and the system can generate multiple gene predictions, annotate the genes, and link these genes within the known orthogroups of the system (preserving their privacy for these genes if desired).  Presumably this sort of thing would be easier as a standalone in-house for the researcher, but web services could also be the place for this.

For fungal-sized genomes this amount of data is not too extereme.  Things like Genome Browser, BLAST, etc should all be rolled out of the box based on the basic builds.

On the DIY and community annotation front, there would also need to be a layer of community derived annotation that could be layered on all these systems.  I would imagine this both to be for gene structure annotation (genome annotation) and functional annotation (protein X does Y based on experiment Z, here is the journal reference).  I think aspects of this would be visible, auditable (tracked), but maybe not blessed as official until a curator could oversee these inputs. In my mind, whether or not this is in a Wiki per se or just new system that allows community input is less important to me than having it be a) structured (not a bunch of free text) b) tracked and versionable c) easy for researchers to input so that the knowledge is captured, even if it has to be reorganized later on.

Seems like a lot of work to be done, but really many of these things already exist through what  the GMOD project has built.  Many loose ends and software that doesn’t fully meet up to these needs, but I think the important concept is these are all general solutions that will be of benefit to most communities, not just the fungal ones.  One lingering question I always have when approaching genomic datas

that will be dynamic, what if any of this makes its way into GenBank?  How is this sort of thing banked so that it can be captured, and does the improved functional or gene structure annotation ever make its way into the repository databases to correct and improve what has already been submitted there?

Cochliobolus genome released

Just noticed that the JGI has released the Cochliobolus heterostrophus genome sequence at their site predicting 9,633 protein-coding genes.  Torrey Mesa Research Institute had access to a sequence many years ago, but it isn’t until now that public version of this genome is available.  Cochliobolus is has been a model plant pathogen system and its production of T-Toxin by a PKS gene (Yang et al).

Penicillium marneffei project

P.marneffeiWe’re excited that a Penicillium marneffei grant to Mat Fisher and collaborators has been funded by the Welcome Trust. It includes a collaboration with Bignell Lab at Imperial College, our lab, JCVI, and Univ of Melbourne. This project will explore functional and comparative genomics approaches to studying the fungus which primarily infects immune compromised individuals in south-east asia where it is found associated with bamboo rats

Scientists at Imperial College London have received almost £350 000 from the Wellcome Trust, the UK’s largest medical research charity, to study Penicillium marneffei, the only Penicillium fungus to cause serious disease in humans. The researchers aim to find out what makes this particular fungus pathogenic.

Read the rest of the release.

Trichoderma reesei genome paper published

TrichodermaThe Trichoderma reesei genome paper was recently published in Nature Biotechnology from Diego Martinez at LANL with collaborators at JGI, LBNL, and others. This fungus was chosen for sequencing because it was found on canvas tents eating the cotton material suggesting it may be a good candidate for degrading cellulose plant material as part of cellulosic ethanol or other biofuels production.  The fungus also has starring roles in industrial processes like making stonewashed jeans due to its prodigious cellulase production.

The most surprising findings from the paper include the fact that there are so few members of some of the enzyme families even though this fungus is able to generate enzymes with so much cellulase activity. The authors found that there is not a significantly larger number of glucoside hydrolases which is a collection of carbohydrate degrading enzymes great for making simple sugars out of complex ones. In fact, several plant pathogens compared (Fusarium graminearum and Magnaporthe grisea) and the sake fermenting Aspergillus oryzae all have more members of this family than does.  T. reesei has almost the least (36) copies of a cellulose binding domain (CBM) of any of the filamentous ascomycete fungi.  They used the CAZyme database (carbohydrate active enzymes) database which has done a fantastic job building up profiles of different enzymes involved in carhohydrate degradation binding, and modifications.

Whether T. reesei is really the best cellulose degrading fungus is definitely an open question.  That it works well in the industrial culture that it has been utilized in is important, but there may be other species of fungi with improved cellulase activity and who may in fact have many more copies of cellulases.  So it will be good to add other fungi to the mix with quantitative information about degradation to try and glean what are the most important combination of enzymes and activities.

One technical note.  The comparison of copy number differences employed in the paper is a simple enough Chi-Squared, work that I’ve done with Matt Hahn and others include a gene family size comparison approach that also taked into account phylogenetic distances and assumes a birth-death process of gene family size change.  It would be great to apply the copy number differences through this or other approaches that just evaluate gene trees for these domains to see where the differences are significant and if they can be polarized to a particular branch of the tree.

So will this genome sequence lead to cheaper, better biofuel production? Certainly it provides an important toolkit to start systematically testing individual cellulase enzymes. It’s hard to say how fast this will make an impact, but the work of JBEI and a host of other research groups and biotech companies are going to be able to systematically test out the utility of these individual enzymes.

There is also evolutionary work by other groups on the evolution of these Hypocreales fungi trying to better define when biotrophic and heterotrophic transitions occurred to sample fungi with different lifestyles that might have different cellulase enyzmes that may not have been observed. Defining the relationships of these fungi and when and how many times transitions to lifestyles occurred to choose the most diverse fungi may be an important part of discovering novel enzymes.

Also see

Martinez, D., Berka, R.M., Henrissat, B., Saloheimo, M., Arvas, M., Baker, S.E., Chapman, J., Chertkov, O., Coutinho, P.M., Cullen, D., Danchin, E.G., Grigoriev, I.V., Harris, P., Jackson, M., Kubicek, C.P., Han, C.S., Ho, I., Larrondo, L.F., de Leon, A.L., Magnuson, J.K., Merino, S., Misra, M., Nelson, B., Putnam, N., Robbertse, B., Salamov, A.A., Schmoll, M., Terry, A., Thayer, N., Westerholm-Parvinen, A., Schoch, C.L., Yao, J., Barbote, R., Nelson, M.A., Detter, C., Bruce, D., Kuske, C.R., Xie, G., Richardson, P., Rokhsar, D.S., Lucas, S.M., Rubin, E.M., Dunn-Coleman, N., Ward, M., Brettin, T.S. (2008). Genome sequencing and analysis of the biomass-degrading fungus Trichoderma reesei (syn. Hypocrea jecorina). Nature Biotechnology DOI: 10.1038/nbt1403

More RIP without sex?

In followup to the Aspergillus RIP paper discussion, Jo Anne posted in the comments that her paper published in FGB about RIP in another asexual species of fungi also found that evidence for the meiosis-specific process of Repeat Induced Point-mutations (RIP).

Continue reading More RIP without sex?

Cryptococcus species deliniation

ResearchBlogging.org What delineates species boundaries in fungi? Much work has been done on biological and phylogenetic species concepts in fungi. Some concepts are reviewed in Taylor et al 2006 and in Taylor et al 2000, and applications can be seen in several pathogens such as Paraccocidiodies, Coccidioides, and the model filamentous (non-pathogenic) fungus Neurospora.

A paper in Fungal Genetics and Biology on species definitions in Cryptococcus neoformans from multi-locus sequencing seeks to provide additional treatment of the observed diversity. A large study of 117 Cryptococcus isolates were examined through multi-locus sequencing (6 loci) and identified two monophyletic lineages within C. neoformans varieties that correspond to var. neoformans and var. grubii. However within the C. gattii samples they identified four monophyletic groups consistent with deep divergences observed from whole genome trees for two strains of C. gattii, MLST, and AFLP studies. By first defining species, we can now test whether any of the species groups have different traits including prevalence in clinical settings and in nature.

BOVERS, M., HAGEN, F., KURAMAE, E., BOEKHOUT, T. (2007). Six monophyletic lineages identified within Cryptococcus neoformans and Cryptococcus gattii by multi-locus sequence typing. Fungal Genetics and Biology DOI: 10.1016/j.fgb.2007.12.004

Phytopathogenic Fungi: what have we learned from genome sequences?

ResearchBlogging.orgA review in Plant Cell from Darren Soanes and colleagues summarizes some of the major findings about evolution of phytopathogenic fungi gleaned from genome sequencing highlighting 12 fungi and 2 oomycetes. By mapping evolution of genes identified as virulence factors as well as genes that appear to have similar patterns of diversification, we can hope to derive some principals about how phytopathogenic fungi have evolved from saprophyte ancestors.

They infer from phylogenies we’ve published (Fitzpatrick et al, James et al) that plant pathogenic capabilities have arisen at least 5 times in the fungi and at least 7 times in the eukaryotes. In addition they use data on gene duplication and loss in the ascomycete fungi (Wapinski et al) to infer there large numbers of losses and gains of genes have occurred in fungal lineages.

Continue reading Phytopathogenic Fungi: what have we learned from genome sequences?

Candida White-Opaque switching

Blogging on Peer-Reviewed ResearchA paper in PLoS Biology from Sandy Johnson’s lab entitled “Interlocking Transcriptional Feedback Loops Control White-Opaque Switching in Candida albicans discusses phenotype switching in the human pathogenic fungus Candida albicans. Why is the important?

“White-opaque switching is an epigenetic phenomenon, where genetically identical cells can exist in two distinctive cell types, white and opaque. Each cell type is stably inherited for many generations, and switching between the two types of cells occurs stochastically and rarely—roughly one switch in 10^4 cell divisions”

white-opaque coloniesThere is also a review by Kira O’Day to discuss the implications of the findings. Understanding this sort of developmental and epigenetic signaling is important to better know how fungi adjust and interact with their environment. However, the authors do conclude that White-Opaque switching is exclusive to Candida albicans so aspects of this research only directly applicable to studies in this system. Phenotype switching is an active area of research for Candida biologists – some nice micrographs and SEM of the different cell morphologies can be seen at Prof. Joachim Morschhäuser’s page (and linked to the right).

Continue reading Candida White-Opaque switching