Aspergillus fumigatus colony growth perturbed upon drug exposure. Are lncRNAs involved in antifungal drug response? (photo credit: Darren Thomson)
One of the greatest threats facing global wheat production is the disease, Septoria tritici Blotch, which is caused by the fungus Zymoseptoria tritici. In Europe alone, Z. tritici is responsible for up to 700 million worth of wheat yield loss annually, and an estimated 70% of the total annual fungicide usage is targeted against it. Z. tritici can rapidly evolve resistance in the field and so novel management strategies are urgently required.
Circadian clocks are molecular machineries which are entrained by environmental signals, such as light and temperature, and which regulate key life processes. The aim of this project is to understand whether the circadian clock regulates pathogenicity and development in Z. tritici.
Z. tritici is responsible for up to 700 million worth of wheat yield loss annually, and an estimated 70% of the total annual fungicide usage is against it, with consequent risk of resistance.
Our initial results demonstrated that Z. tritici can detect light, and that this signal influences vegetative growth. We therefore hypothesised that light could be a primary input which regulates the circadian clock of the pathogen.
In the model fungus Neurosopora crassa, the circadian clock is encoded by the three genes white collar-1 (wc-1), white collar-2 (wc-2) and frequency (frq). Our bioinformatic analyses identified homologs in Z. tritici to all three of the N. crassa genes, and these were designated ztwco-1, ztwco-2 and ztfrq. Yeast-two hybrid assays demonstrated that the ZTWCO-2 and ZTWCO-2 proteins interact; a result which is also similar to observations from N. crassa.
In order to understand the role of the putative circadian clock genes in Z. tritici, we generated deletion mutants. Our results to date show that deletion of some of these candidate genes causes defects in vegetative growth, but that the mutants are still able to infect the wheat host.
This is the first in-depth study of the circadian clock in Z. tritici, and our findings open up multiple avenues for future investigation. The long-term aim of this research is to inform future control strategies against Z. tritici, such as timing of fungicide application and identification of novel targets for future fungicide screens.
Anna Tiley is a Government of Ireland Postdoctoral Fellow based in the School of Agriculture and Food Science at University College Dublin, Ireland. She holds a degree in Biological Science from the University of Oxford, and a PhD in Molecular Plant Pathology from the University of Bristol. Anna has over seven years experience working with the wheat pathogen Zymoseptoria tritici, and her research focuses on the genetic basis of development and pathogenicity in this species. Follow on Twitter @tileyanna
I am fascinated by the way how diverse microbial species in the environment establish various modes of molecular interplay. That leads to the formation of complex microbial communities which make remarkable contributions to biogeochemical cycles, biotechnology and maintaining ecosystems.
Our group at the University of Tsukuba, steered under the guidance of Professor Norio Takeshita, contemplates the aspects of reciprocity in environmental microbial communities.
Bacterial-fungal interactions are crucial for understanding the microbial ecosystems that are closely related to agriculture, medicine and the environment.
Currently, our focus falls on fungi and bacteria which comprise a large fraction of the overall soil biomass. Bacterial-fungal interactions are crucial for the understanding of microbial ecosystems that is closely related to agriculture, medicine and the environment.
It is well known that microbial interactions are promoting the activation of cryptic biosynthetic pathways, thereby leading to the production of secondary metabolites. Those metabolites possess not only defense functions but also steer cell to cell communication and other interactive dynamics. However, the majority of studies based on the dynamics of microbiota have used monocultures.
Co-culturing has been proven to be an effective method to mimic conditions existing among microbial interactions within nature. Hence this approach may potentially facilitate the production of novel antimicrobials as well as facilitator molecules.
Together with Momoka Kuchira we were able to characterize the mutualistic relationship between the filamentous fungus Aspergillus nidulans and the gram-positive bacterium Bacillus subtilis (currently under review). Our studies provide evidence of their spatial and metabolic interaction that facilitate inter-species communication thereby exploring untraveled environmental niches and obtaining nutrients. It is understandable that there are extensive untraveled territories of microbial communities. Hence, our next milestone was to further exploit this prospect.
We conducted growth experiments of different combinations of fungal and bacterial species in coculture in selected nutrient rich and minimal conditions to observe the interactive dynamics of bacteria and fungi.
(I) Co-culture of Fungi and Bacteria on solid media. (II & III) Dispersal of bacterial cells (fluorescence) on fungal hyphae. (IV) SEM image denoting fungal-bacterial interaction.
Cocultures were incubated for 1 day up to 4 days prior to microscope imaging. An array of parameters such as velocity of the movement of bacterial cells, travel distance, colonization degree and growth rate were considered to define the specificity of interaction. According to the degree of these interactions and dynamics the combinations were classified into positive, negative and neutral genres.
A selected array of combinations was subjected to LC-MS and tandem spectroscopic analysis and the differences of chemical profiles of pure and co cultures have been analyzed to determine and contrast the production levels of bioactive compounds. By chemically defining the bioactive compounds we subsequently observed the transcriptomic and genomic expression to establish an inference of their genomic potential in the state of co-existence.
We are certain that this approach would gain a more reliable perspective on the ecological context of environmental microbiota in their natural setting. Moreover, it would aid in economical and societal aspects such as bio control and therapeutic value as well as in new possible avenues for yielding antimicrobial compounds.
Gayan Abeysinghe is a graduate student in Microbiology Research Center for Sustainability, Graduate School of Life and Environmental Sciences at the University of Tsukuba, Japan. Gayans research focus directs to impart insights on the microbial communication in the community setting and aims to the discovery and development of novel antimicrobials with better efficiency.
lncRNA remained relatively elusive until sequencing exploded, with the discovery of genomes with small numbers of genes and surprising amounts of junk being transcribed.
In the 1960s, DNA not coding for protein was termed junk DNA. It took another three decades before we begun to understand the gene regulatory potential of this so-called rubbish. In the 1990s, studies discovered small noncoding RNA able to silence gene translation via RNA interference. At this time, a group termed long noncoding RNA (lncRNA) were also uncovered.
Human lncRNAs such as the X chromosome-silencer, Xist, emerged first. Mechanisms included regulating gene expression by altering local epigenetics or by guiding proteins to distant genes. However, lncRNA remained relatively elusive until sequencing exploded, and we were suddenly faced with genomes with unexpectedly small numbers of genes and surprising amounts of junk being transcribed.
Aspergillus fumigatus colony growth perturbed upon drug exposure (photo credit: Darren Thomson).
We now know of numerous regulatory lncRNA which deploy a variety of mechanisms in animals, plants and fungi. For example, Neurospora crassa produces over 2500 lncRNA. However, in the human pathogen, Aspergillus fumigatus, only a handful are known. I sought to uncover A. fumigatus lncRNA and hypothesised that they could influence its response to antifungal drugs.
Using drug exposure RNAseq experiments and a bioinformatics pipeline, we identified over 3000 lncRNA candidates. I was surprised to find over 500 lncRNA were significantly expressed upon exposure to a frontline antifungal, itraconazole. Clustering analysis showed that the lncRNA display similar dose-responsive expression patterns to genes, suggesting these lncRNA are not transcriptional noise. Instead, they are co-ordinately regulated features which may play a role in the A. fumigatus drug response.
Further investigation into these novel lncRNA may inform our understanding of antifungal drug resistance mechanisms.
Danielle Weaver is a postdoctoral researcher at the Manchester Fungal Infection Group at the University of Manchester, UK. She completed her PhD on glycosylation in the foodborne bacterial pathogen, Campylobacter jejuni, but has since shifted focus to work on fungal pathogens. Her current research aims to harness next generation sequencing technologies to develop pathogen and drug resistance diagnostics and investigate RNA biology in Aspergillus fumigatus. Follow on Twitter@dan_weaver1@UofMMFIG
I have developed synthetic biology based-tools for scalable regulation or activation of transcriptionally silent secondary metabolite (SM) gene clusters in filamentous fungi.
Filamentous fungi produce a large variety of interesting SMs, molecules that are not essential for growth, but typically possess bioactivities that are of great value to medicine, agriculture and manufacturing. Many of these SM gene clusters are not expressed under laboratory conditions and may need to be activated or heterologously expressed before the desired products can be obtained.
Synthetic biology has revolutionized metabolic engineering and brings the exploitation of industrial microorganisms to a new level by enabling fine-tuning of gene expression allows the control of entire pathways.
Although filamentous fungi are attracting increasing interest as biotechnological production hosts, efficient genetic tools for their exploitation are limited.
Our work represents the development of synthetic gene regulatory devices, that enables scalable expression of a target gene, ranging from hardly detectable to a level similar to that of highest expressed native genes. Synthetic promoters, which were transcriptionally silent on their own, could be activated at desired level by the introduction of binding sites for the synthetic transcription factor (STF). A gene cluster may require expression levels tuned individually for each gene which is a great advantage provided by this system.
Fluorescence microscopy image of hyphae of a fungal strain expressing fluorescent reporters (STF-GFP-NLS, RFP-SKL).
In the STF, the DNA-binding domain of the qa-1F transcription factor from Neurospora crassa is fused to the VP16 activation domain. This STF controls the expression of genes under control of a synthetic promoter containing quinic acid upstream activating sequence (QUAS) binding elements. Control devices were characterized with respect to three main features: expression of the STF, number of QUAS elements, and the type of core promoter used downstream of the QUAS element.
The versatility of the control device was demonstrated by fluorescent reporters and its application was confirmed by synthetically controlling the penicillin gene cluster in Penicillium chrysogenum for antibiotic production. We anticipate that these well-characterized and robustly performing control devices will be useful tools for silent SM gene cluster activation and for development of filamentous fungi as production hosts.
Lszl Mzsik is a fourth-year PhD student in the laboratory of Arnold Driessen at the University of Groningen, the Netherlands. Within the Horizon 2020 Marie Skodowska-Curie COFUND ALERT program, his project aims at developing new genetic tools for the discovery of novel antibacterial compounds in fungi to tackle the increasing problem of multi-drug resistant bacteria.
View original post here:
Scientists of the future at the 15th European Conference on Fungal Genetics - On Biology - BMC Blogs Network
- 1st draft of a human 'pangenome' published, adding millions of ... - May 17th, 2023
- A Brief Guide to Genomics - National Human Genome Research Institute - May 17th, 2023
- Human genetics - Immunogenetics | Britannica - April 23rd, 2023
- A Troublesome Inheritance - Wikipedia - April 23rd, 2023
- Human - Simple English Wikipedia, the free encyclopedia - January 29th, 2023
- Human Genetics and Genomics Training Program - Hopkins Medicine - January 4th, 2023
- Genetics vs. Genomics Fact Sheet - Genome.gov - December 18th, 2022
- Human Genetics and Molecular Biology, PhD - Johns Hopkins University - December 18th, 2022
- Race (human categorization) - Wikipedia - December 2nd, 2022
- Human Y-chromosome DNA haplogroup - Wikipedia - November 24th, 2022
- Abstracts | International Congress of Human Genetics 2023 - November 24th, 2022
- Human genetic variation - Wikipedia - November 6th, 2022
- Genetics | The Smithsonian Institution's Human Origins Program - October 29th, 2022
- Fluent BioSciences showcasing breakthrough solutions to enable unprecedented scale, cost-efficiency and access for single-cell RNA sequencing at the... - October 29th, 2022
- Researchers seek to unravel the mystery of susceptibility to drug addiction - Newswise - October 4th, 2022
- NIH initiative to systematically investigate and establish function of every human gene - National Institutes of Health (.gov) - October 4th, 2022
- ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma | Communications Biology - Nature.com - October 4th, 2022
- Does obesity have more to do with the brain than we initially thought? - Medical News Today - October 4th, 2022
- Who will get the call from Stockholm? It's time for STAT's 2022 Nobel Prize predictions - STAT - October 4th, 2022
- Solving medical mysteries: Physicians and researchers collaborate to study the most challenging cases - AAMC - October 4th, 2022
- Mystery gene matures the skeleton of the cell - EurekAlert - October 4th, 2022
- What Is The Most Important factor Driving The Global Human Genetics Market? - PharmiWeb.com - September 25th, 2022
- How Africa's genetic diversity can be harnessed to close the continent's 'drug and treatment gap' - Genetic Literacy Project - September 25th, 2022
- Ability to move to the pulse of music has genetic link - DTNEXT - September 25th, 2022
- Is the Spike Protein Changing Our Gene Expression? - The Epoch Times - September 25th, 2022
- How prehistoric DNA is helping to unlock the secrets of human evolution - EL PAS USA - September 25th, 2022
- Personalised medicine and the advantages of big data and AI-based diagnostics - Medical Device Network - September 25th, 2022
- Viewpoint: In the post Roe v Wade world, what changes should a biology textbook writer make to address the medical repercussions of Dobbs? - Genetic... - September 25th, 2022
- Bears' ability to regulate insulin narrowed down to eight proteins WSU Insider - WSU News - September 25th, 2022
- Sex, Selection and Biodiversity - Syracuse.edu - Syracuse University - September 25th, 2022
- Was the Russian Flu the first coronavirus pandemic? Find out at next Science Caf - University of Nebraska at Kearney - September 25th, 2022
- University of Chicago South Side Science Fest created to show off the fun, myriad pathways into field. - Chicago Tribune - September 25th, 2022
- The genetics of human personality - PubMed - August 14th, 2022
- Genetics - The Harvey Institute for Human Genetics - GBMC HealthCare in ... - August 14th, 2022
- Degrees of the Future 2022: Genetics - Gizmodo - August 14th, 2022
- U of U Health-Led Research Awarded $28 Million to Explore HIV's Inner Workings and Vulnerabilities - University of Utah Health Care - August 14th, 2022
- Revisiting Companies That Had Their IPO in 2018 - Investment U - August 14th, 2022
- Monkeypox Myth Busting: Here's What You Need to Know - The Mighty - August 14th, 2022
- Relay Therapeutics Reports Second Quarter 2022 Financial Results and Corporate Highlights - Yahoo Finance - August 5th, 2022
- Baylor receives NCI grant to study liver cancer risk and prevention - Baylor College of Medicine News - August 5th, 2022
- Whole Exome Sequencing Market reach a valuation of US$ 4,256.30 Mn, at a CAGR of 19.24% in the Forecast 2030 - BioSpace - August 5th, 2022
- Mendels Genetic Revolution and the Legacy of Scientific Racism - NewsClick - August 5th, 2022
- AMGEN TO ACQUIRE CHEMOCENTRYX FOR $4 BILLION IN CASH - BioSpace - August 5th, 2022
- Cotton Buds Market Value Is Estimated to Reach USD 747.16 BN By 2028, With 3.2% CAGR Credence Research - Digital Journal - August 5th, 2022
- Verve Therapeutics Shares Up 84%; ARKG Offers Exposure - ETFdb.com - July 27th, 2022
- Double up on the guac? Those avocados are good for your heart health - American Heart Association - July 27th, 2022
- Extending the PAX1 spectrum: a dominantly inherited variant causes oculo-auriculo-vertebral syndrome | European Journal of Human Genetics - Nature.com - July 27th, 2022
- Scientists Unravel the Mystery of Junk Genes That Are Key to Brain Development - SciTechDaily - July 27th, 2022
- COVID-19 Can Make the Brain Age by 2 Decades; Here's 1 Way to Reverse Aging - The Epoch Times - July 27th, 2022
- Mice Model Market Forecast to 2028 - COVID-19 Impact and Global Analysis By Type, Service, Technology, Indication, End User, Application, and Mode -... - July 27th, 2022
- Master's Degree in Human Genetics | Human Genetics | Michigan Medicine ... - July 11th, 2022
- Here's how the $100 Human Genome will Change Medicine - BioSpace - July 11th, 2022
- Genomic medicine: the role of the nursing workforce - Nursing Times - July 11th, 2022
- AbbVie Half Breaks Up with Alector on Alzheimer's - BioSpace - July 11th, 2022
- The human identification market size is projected to reach - GlobeNewswire - July 11th, 2022
- Global wheat production can be doubled to feed millions and save land, say scientists - Sky News - July 11th, 2022
- Huntsville native among TIMEs 100 most influential people - WHNT News 19 - July 3rd, 2022
- New hope for IVF patients as global study published in Human Reproduction shows AI can effectively assess genetic integrity of embryos - Yahoo Finance - July 3rd, 2022
- A Week At The Most Secretive Conference On Aging - Forbes - July 3rd, 2022
- Human genetics shape the gut microbiome - PMC - June 13th, 2022
- expert reaction to a conference abstract on retinal screening predicting risk of myocardial infarction - Science Media Centre - June 13th, 2022
- New Comprehensive Map Ties Every Human Gene to Its Function - SciTechDaily - June 13th, 2022
- Buffalo shooters manifesto quoted a university researcher. Thats raising questions about racism in academia - Yahoo News - June 13th, 2022
- Thalidomide could be used as a therapeutic for AVMs - Cosmos - June 13th, 2022
- How Electric Fish Were Able to Evolve Electric Organs - UT News - University of Texas - June 4th, 2022
- Survival of the Best: The Past, Present and Future of Plants - CSRwire.com - June 4th, 2022
- AMGEN ANNOUNCES WEBCAST OF 2022 JEFFERIES HEALTHCARE CONFERENCE | News | wfmz.com - 69News WFMZ-TV - June 4th, 2022
- Experts Discover New Disease Caused by Faulty Genes Affecting the Kidney and Liver: Newcastle University Study - Nature World News - June 4th, 2022
- At-Home Colorectal Cancer Testing and Follow-Up Vary by Ethnicity - Medscape - June 4th, 2022
- Who is your real parent? Our Father on Netflix depicts the dark side of 'secret serial sperm donation'. My birth has a similar origin but with a more... - June 4th, 2022
- Autism and the complete human genome: Q&A with Evan Eichler | Spectrum - Spectrum - May 15th, 2022
- Increased Mutations in Children Can Be Traced Back to Mistakes in Father's Sperm - Neuroscience News - May 15th, 2022
- Not All Is Rosy For The Pink Pigeon - Eurasia Review - May 15th, 2022
- Why haven't we cloned a human yet? - Livescience.com - May 15th, 2022
- Study probes the relationship between genetics, proteins, and disease risk - The Hub at Johns Hopkins - May 15th, 2022
- Singular Genomics Announces Formation of Scientific Advisory Board - BioSpace - May 15th, 2022
- COVID Resistance Might Be Tied To Genetics: Experts - Medical Daily - May 15th, 2022
- Letter: Why no to Roe and abortion - INFORUM - May 15th, 2022
- Gut Microbiome Composition Predictive of Patient Response to Statins - Business Wire - May 15th, 2022
- Finding A Place In Science - Texas A&M Today - Texas A&M University Today - May 15th, 2022