Michael-Shawn Fletcher

Biogeochemical Responses to Holocene Catchment-Lake Dynamics in the Tasmanian World Heritage Area, Australia

Publisher: American Geophysical Union (AGU)

Date: 05-2018

DOI: 10.1029/2017JG004136

An evolutionary conserved interaction between the Gcm transcription factor and the SF1 nuclear receptor in the female reproductive system.

Publisher: Springer Science and Business Media LLC

Date: 25-11-2016

DOI: 10.1038/SREP37792

Abstract: NR5A1 is essential for the development and for the function of steroid producing glands of the reproductive system. Moreover, its misregulation is associated with endometriosis, which is the first cause of infertility in women. Hr39, the Drosophila ortholog of NR5A1, is expressed and required in the secretory cells of the spermatheca, the female exocrine gland that ensures fertility by secreting substances that attract and capacitate the spermatozoids. We here identify a direct regulator of Hr39 in the spermatheca: the Gcm transcription factor. Furthermore, lack of Gcm prevents the production of the secretory cells and leads to female sterility in Drosophila. Hr39 regulation by Gcm seems conserved in mammals and involves the modification of the DNA methylation profile of mNr5a1 . This study identifies a new molecular pathway in female reproductive system development and suggests a role for hGCM in the progression of reproductive tract diseases in humans.

The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled.

Publisher: eLife Sciences Publications, Ltd

Date: 14-10-2016

DOI: 10.7554/ELIFE.15983

Abstract: Collective migration is a complex process that contributes to build precise tissue and organ architecture. Several molecules implicated in cell interactions also control collective migration, but their precise role and the finely tuned expression that orchestrates this complex developmental process are poorly understood. Here, we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the developing Drosophila wing. Frazzled expression is induced by the transcription factor Glide/Gcm in a dose-dependent manner. Thus, the glial determinant also regulates the efficiency of collective migration. NetrinB but not NetrinA serves as a chemoattractant and Unc5 contributes as a repellant Netrin receptor for glia migration. Our model includes strict spatial localization of a ligand, a cell autonomously acting receptor and a fate determinant that act coordinately to direct glia toward their final destination.

The Drosophila fragile X mental retardation protein participates in the piRNA pathway.

Publisher: The Company of Biologists

Date: 06-2015

DOI: 10.1242/JCS.161810

Abstract: RNA metabolism controls multiple biological processes, and a specific class of small RNAs, called piRNAs, act as genome guardians by silencing the expression of transposons and repetitive sequences in the gonads. Defects in the piRNA pathway affect genome integrity and fertility. The possible implications in physiopathological mechanisms of human diseases have made the piRNA pathway the object of intense investigation, and recent work suggests that there is a role for this pathway in somatic processes including synaptic plasticity. The RNA-binding fragile X mental retardation protein (FMRP, also known as FMR1) controls translation and its loss triggers the most frequent syndromic form of mental retardation as well as gonadal defects in humans. Here, we demonstrate for the first time that germline, as well as somatic expression, of Drosophila Fmr1 (denoted dFmr1), the Drosophila ortholog of FMRP, are necessary in a pathway mediated by piRNAs. Moreover, dFmr1 interacts genetically and biochemically with Aubergine, an Argonaute protein and a key player in this pathway. Our data provide novel perspectives for understanding the phenotypes observed in Fragile X patients and support the view that piRNAs might be at work in the nervous system.

Centennial and millennial‐scale dynamics in Araucaria–Nothofagus forests in the southern Andes

Publisher: Wiley

Date: 30-11-2020

DOI: 10.1111/JBI.14017

New insights in the clockwork mechanism regulating lineage specification: Lessons from the Drosophila nervous system.

Publisher: Wiley

Date: 11-12-2015

DOI: 10.1002/DVDY.24228

Abstract: Powerful transcription factors called fate determinants induce robust differentiation programs in multipotent cells and trigger lineage specification. These factors guarantee the differentiation of specific tissues/organs/cells at the right place and the right moment to form a fully functional organism. Fate determinants are activated by temporal, positional, epigenetic, and post-transcriptional cues, hence integrating complex and dynamic developmental networks. In turn, they activate specific transcriptional/epigenetic programs that secure novel molecular landscapes. In this review, we use the Drosophila Gcm glial determinant as a model to discuss the mechanisms that allow lineage specification in the nervous system. The dynamic regulation of Gcm via interlocked loops has recently emerged as a key event in the establishment of stable identity. Gcm induces gliogenesis while triggering its own extinction, thus preventing the appearance of metastable states and neoplastic processes. Using simple animal models that allow in vivo manipulations provides a key tool to disentangle the complex regulation of cell fate determinants.

L’hétérogénéité insoupçonnée du système immunitaire de la drosophile

Publisher: EDP Sciences

Date: 2021

DOI: 10.1051/MEDSCI/2020251

Temporal specificity and heterogeneity of the fly immune cells’ transcriptional landscape

Publisher: Cold Spring Harbor Laboratory

Date: 20-12-2019

DOI: 10.1101/2019.12.20.871301

Abstract: Immune cells provide defense against the non-self, however recent data suggest roles well beyond innate immunity, in processes as erse as development, metabolism and tumor progression. Nevertheless, the heterogeneity of these cells remains an open question. Using bulk RNA sequencing we find that the Drosophila immune cells (hemocytes) display distinct features in the embryo, a closed and rapidly developing system, compared to the larva, which is exposed to environmental and metabolic challenges. Through single cell RNA sequencing we identify fourteen hemocyte clusters present in unchallenged larvae and associated with distinct cellular processes e.g. proliferation, phagocytosis, metabolic homeostasis and humoral response. Finally, we characterize the changes occurring in the hemocyte clusters upon wasp infestation that triggers the differentiation of a novel cell type, the lamellocyte. This first molecular atlas provides precious insights and paves the way to study the biology of the Drosophila immune cells in physiological and pathological conditions.

Evidence for reduced environmental variability in response to increasing human population growth during the late Holocene in northwest Tasmania, Australia

Publisher: Elsevier BV

Date: 10-2018

DOI: 10.1016/J.QUASCIREV.2018.07.001

Tailoring the immune response to the availability of nutrients

Publisher: Wiley

Date: 13-04-2020

DOI: 10.1111/FEBS.15304

The Repo Homeodomain Transcription Factor Suppresses Hematopoiesis inDrosophilaand Preserves the Glial Fate

Publisher: Society for Neuroscience

Date: 30-11-2019

DOI: 10.1523/JNEUROSCI.1059-18.2018

Abstract: Despite their different origins, Drosophila glia and hemocytes are related cell populations that provide an immune function. Drosophila hemocytes patrol the body cavity and act as macrophages outside the nervous system, whereas glia originate from the neuroepithelium and provide the scavenger population of the nervous system. Drosophila glia are hence the functional orthologs of vertebrate microglia, even though the latter are cells of immune origin that subsequently move into the brain during development. Interestingly, the Drosophila immune cells within (glia) and outside (hemocytes) the nervous system require the same transcription factor glial cells deficient/glial cells missing (Glide/Gcm) for their development. This raises the issue of how do glia specifically differentiate in the nervous system, and hemocytes in the procephalic mesoderm. The Repo homeodomain transcription factor and panglial direct target of Glide/Gcm is known to ensure glial terminal differentiation. Here we show that Repo also takes center stage in the process that discriminates between glia and hemocytes. First, Repo expression is repressed in the hemocyte anlagen by mesoderm-specific factors. Second, Repo ectopic activation in the procephalic mesoderm is sufficient to repress the expression of hemocyte-specific genes. Third, the lack of Repo triggers the expression of hemocyte markers in glia. Thus, a complex network of tissue-specific cues biases the potential of Glide/Gcm. These data allow us to revise the concept of fate determinants and help us to understand the bases of cell specification. Both sexes were analyzed. SIGNIFICANCE STATEMENT Distinct cell types often require the same pioneer transcription factor, raising the issue of how one factor triggers different fates. In Drosophila , glia and hemocytes provide a scavenger activity within and outside the nervous system, respectively. While they both require the glial cells deficient/glial cells missing (Glide/Gcm) transcription factor, glia originate from the ectoderm, and hemocytes from the mesoderm. Here we show that tissue-specific factors inhibit the gliogenic potential of Glide/Gcm in the mesoderm by repressing the expression of the homeodomain protein Repo, a major glial-specific target of Glide/Gcm. Repo expression in turn inhibits the expression of hemocyte-specific genes in the nervous system. These cell-specific networks secure the establishment of the glial fate only in the nervous system and allow cell ersification.

The loss of an indigenous constructed landscape following British-invasion of Australia: an insight in to the deep human imprint on the Australian landscape. AMBIO: A Journal of the Human Environment

Publisher: Springer Science and Business Media LLC

Date: 06-05-2020

DOI: 10.1007/S13280-020-01339-3

Author response: Embryonic hematopoiesis modulates the inflammatory response and larval hematopoiesis in Drosophila

Publisher: eLife Sciences Publications, Ltd

Date: 04-06-2018

DOI: 10.7554/ELIFE.34890.029

Early Cholecystectomy Is Superior to Delayed Cholecystectomy for Acute Cholecystitis: a Meta-analysis

Publisher: Springer Science and Business Media LLC

Date: 07-03-2015

DOI: 10.1007/S11605-015-2747-X

Abstract: The timing of laparoscopic cholecystectomy for acute cholecystitis remains an issue for debate amongst general surgeons. The aim of this study was to compare clinical outcomes between early and delayed cholecystectomy for acute cholecystitis. The primary outcome measures included mortality rates, complication rates, length of hospital stay and conversion rates to open procedures. A search of electronic databases was performed for randomised controlled trials. Fifteen studies were included. Early surgery has a decreased risk of wound infections (RR 0.57, 95 % CI 0.35-0.93, p=0.01) compared with delayed surgery but no difference in mortality, bile duct injuries, bile duct leaks and the risk of conversion to open surgery. Of patients in the delayed group, 9.7 % failed initial non-operative management and underwent emergency LC. Early surgery had a significantly reduced total hospital stay and mean hospital costs compared with delayed surgery. Early laparoscopic cholecystectomy in acute cholecystitis demonstrated decreased incidence of wound infections, a shorter total length of stay and decreased costs with no difference in the rates of mortality, bile duct injuries, bile leaks and conversions. These results support that early laparoscopic cholecystectomy is the best care and should be considered a routine in patients presenting with acute cholecystitis.

Climate Change Amplifications of Climate‐Fire Teleconnections in the Southern Hemisphere

Publisher: American Geophysical Union (AGU)

Date: 28-05-2018

DOI: 10.1029/2018GL078294

Embryonic hematopoiesis modulates the inflammatory response and larval hematopoiesis in Drosophila

Publisher: eLife Sciences Publications, Ltd

Date: 11-07-2018

DOI: 10.7554/ELIFE.34890

Abstract: Recent lineage tracing analyses have significantly improved our understanding of immune system development and highlighted the importance of the different hematopoietic waves. The current challenge is to understand whether these waves interact and whether this affects the function of the immune system. Here we report a molecular pathway regulating the immune response and involving the communication between embryonic and larval hematopoietic waves in Drosophila. Down-regulating the transcription factor Gcm specific to embryonic hematopoiesis enhances the larval phenotypes induced by over-expressing the pro-inflammatory Jak/Stat pathway or by wasp infestation. Gcm works by modulating the transduction of the Upd cytokines to the site of larval hematopoiesis and hence the response to chronic (Jak/Stat over-expression) and acute (wasp infestation) immune challenges. Thus, homeostatic interactions control the function of the immune system in physiology and pathology. Our data also indicate that a transiently expressed developmental pathway has a long-lasting effect on the immune response.

New age controls on Oligocene and Miocene sediments in southeastern Australia

Publisher: Elsevier BV

Date: 09-2018

DOI: 10.1016/J.REVPALBO.2018.05.003

In cell mutational interference mapping experiment (in cell MIME) identifies the 5' polyadenylation signal as a dual regulator of HIV-1 genomic RNA production and packaging.

Publisher: Oxford University Press (OUP)

Date: 05-03-2018

DOI: 10.1093/NAR/GKY152

Catastrophic bushfires, indigenous fire knowledge and reframing science in Southeast Australia

Publisher: MDPI AG

Date: 09-09-2021

DOI: 10.3390/FIRE4030061

Abstract: The catastrophic 2019/2020 Black Summer bushfires were the worst fire season in the recorded history of Southeast Australia. These bushfires were one of several recent global conflagrations across landscapes that are homelands of Indigenous peoples, homelands that were invaded and colonised by European nations over recent centuries. The subsequent suppression and cessation of Indigenous landscape management has had profound social and environmental impacts. The Black Summer bushfires have brought Indigenous cultural burning practices to the forefront as a potential management tool for mitigating climate-driven catastrophic bushfires in Australia. Here, we highlight new research that clearly demonstrates that Indigenous fire management in Southeast Australia produced radically different landscapes and fire regimes than what is presently considered “natural”. We highlight some barriers to the return of Indigenous fire management to Southeast Australian landscapes. We argue that to adequately address the potential for Indigenous fire management to inform policy and practice in managing Southeast Australian forest landscapes, scientific approaches must be decolonized and shift from post-hoc engagement with Indigenous people and perspectives to one of collaboration between Indigenous communities and scientists.

Northward shift of the southern westerlies during the Antarctic Cold Reversal

Publisher: Elsevier BV

Date: 11-2021

DOI: 10.1016/J.QUASCIREV.2021.107189

Interlocked loops trigger lineage specification and stable fates in the Drosophila nervous system.

Publisher: Springer Science and Business Media LLC

Date: 28-07-2014

DOI: 10.1038/NCOMMS5484

Abstract: Multipotent precursors are plastic cells that generate different, stable fates at the correct number, place and time, to allow tissue and organ formation. While fate determinants are known to trigger specific transcriptional programs, the molecular pathway driving the progression from multipotent precursors towards stable and specific identities remains poorly understood. Here we demonstrate that, in Drosophila neural precursors, the glial determinant glial cell missing (Gcm) acts as a 'time bomb' and triggers its own degradation once the glial programme is stably activated. This requires a sequence of transcriptional and posttranscriptional loops, whereby a Gcm target first affects the expression and then acetylation of the fate determinant, thus controlling Gcm levels and stability over time. Defective homeostasis between the loops alters the neuron:glia ratio and freezes cells in an intermediate glial/neuronal phenotype. In sum, we identify an efficient strategy triggering cell identity, a process altered in pathological conditions such as cancer.

Functional Conservation of the Glide/Gcm Regulatory Network Controlling Glia, Hemocyte, and Tendon Cell Differentiation in Drosophila.

Publisher: Oxford University Press (OUP)

Date: 12-11-2016

DOI: 10.1534/GENETICS.115.182154

Abstract: High-throughput screens allow us to understand how transcription factors trigger developmental processes, including cell specification. A major challenge is identification of their binding sites because feedback loops and homeostatic interactions may mask the direct impact of those factors in transcriptome analyses. Moreover, this approach dissects the downstream signaling cascades and facilitates identification of conserved transcriptional programs. Here we show the results and the validation of a DNA adenine methyltransferase identification (DamID) genome-wide screen that identifies the direct targets of Glide/Gcm, a potent transcription factor that controls glia, hemocyte, and tendon cell differentiation in Drosophila. The screen identifies many genes that had not been previously associated with Glide/Gcm and highlights three major signaling pathways interacting with Glide/Gcm: Notch, Hedgehog, and JAK/STAT, which all involve feedback loops. Furthermore, the screen identifies effector molecules that are necessary for cell-cell interactions during late developmental processes and/or in ontogeny. Typically, immunoglobulin (Ig) domain–containing proteins control cell adhesion and axonal navigation. This shows that early and transiently expressed fate determinants not only control other transcription factors that, in turn, implement a specific developmental program but also directly affect late developmental events and cell function. Finally, while the mammalian genome contains two orthologous Gcm genes, their function has been demonstrated in vertebrate-specific tissues, placenta, and parathyroid glands, begging questions on the evolutionary conservation of the Gcm cascade in higher organisms. Here we provide the first evidence for the conservation of Gcm direct targets in humans. In sum, this work uncovers novel aspects of cell specification and sets the basis for further understanding of the role of conserved Gcm gene regulatory cascades.

The role of species composition in the emergence of alternate vegetation states in a temperate rainforest system

Publisher: Springer Science and Business Media LLC

Date: 16-09-2020

DOI: 10.1007/S10980-020-01110-9

What do you mean, ‘megafire’?

Publisher: Wiley

Date: 03-05-2022

DOI: 10.1111/GEB.13499

Abstract: ‘Megafire’ is an emerging concept commonly used to describe fires that are extreme in terms of size, behaviour, and/or impacts, but the term’s meaning remains ambiguous. We sought to resolve ambiguity surrounding the meaning of ‘megafire’ by conducting a structured review of the use and definition of the term in several languages in the peer‐reviewed scientific literature. We collated definitions and descriptions of megafire and identified criteria frequently invoked to define megafire. We recorded the size and location of megafires and mapped them to reveal global variation in the size of fires described as megafires. We identified 109 studies that define the term ‘megafire’ or identify a megafire, with the term first appearing in the peer‐reviewed literature in 2005. Seventy‐one (~65%) of these studies attempted to describe or define the term. There was considerable variability in the criteria used to define megafire, although definitions of megafire based on fire size were most common. Megafire size thresholds varied geographically from 100–100,000 ha, with fires 10,000 ha the most common size threshold (41%, 18/44 studies). Definitions of megafire were most common from studies led by authors from North America (52%, 37/71). We recorded 137 instances from 84 studies where fires were reported as megafires, the vast majority (94%, 129/137) of which exceed 10,000 ha in size. Megafires occurred in a range of biomes, but were most frequently described in forested biomes (112/137, 82%), and usually described single ignition fires (59% 81/137). As Earth’s climate and ecosystems change, it is important that scientists can communicate trends in the occurrence of larger and more extreme fires with clarity. To overcome ambiguity, we suggest a definition of megafire as fires 10,000 ha arising from single or multiple related ignition events. We introduce two additional terms – gigafire ( 100,000 ha) and terafire ( 1,000,000 ha) – for fires of an even larger scale than megafires.

The changing role of fire in conifer-dominated temperate rainforest through the last 14,000 years

Publisher: Elsevier BV

Date: 02-2018

DOI: 10.1016/J.QUASCIREV.2017.12.023

Variance and Rate-of-Change as Early Warning Signals for a Critical Transition in an Aquatic Ecosystem State: A Test Case From Tasmania, Australia

Publisher: American Geophysical Union (AGU)

Date: 02-2018

DOI: 10.1002/2017JG004135

Toward a Consensus in the Repertoire of Hemocytes Identified in Drosophila

Publisher: Frontiers Media SA

Date: 04-03-2021

DOI: 10.3389/FCELL.2021.643712

Abstract: The catalog of the Drosophila immune cells was until recently limited to three major cell types, based on morphology, function and few molecular markers. Three recent single cell studies highlight the presence of several subgroups, revealing a large ersity in the molecular signature of the larval immune cells. Since these studies rely on somewhat different experimental and analytical approaches, we here compare the datasets and identify eight common, robust subgroups associated to distinct functions such as proliferation, immune response, phagocytosis or secretion. Similar comparative analyses with datasets from different stages and tissues disclose the presence of larval immune cells resembling embryonic hemocyte progenitors and the expression of specific properties in larval immune cells associated with peripheral tissues.

The early life of a fly glial cell.

Publisher: Wiley

Date: 30-07-2016

DOI: 10.1002/WDEV.200

Abstract: Throughout evolution, glia have key regulatory roles in neural development and function. Typically, they control the response to developmental and/or pathological signals, thereby affecting neural proliferation, remodeling, survival, and regeneration. Such complex biology depends on the plastic features of glial cells, but also on the presence of different classes of glial cells, hence the importance of understanding the cellular and the molecular mechanisms underlying their development. The fly community has made major breakthroughs by characterizing the bases of gliogenesis and here we describe the glial lineages as well as the glial promoting factor active in the embryo of Drosophila melanogaster . WIREs Dev Biol 2016, 5:67–84. doi: 10.1002/wdev.200 This article is categorized under: Gene Expression and Transcriptional Hierarchies Cellular Differentiation Invertebrate Organogenesis Flies Nervous System Development Flies

Novel cell- and stage-specific transcriptional signatures defining Drosophila neurons, glia and hemocytes

Publisher: Cold Spring Harbor Laboratory

Date: 07-2022

DOI: 10.1101/2022.06.30.498263

Abstract: Cell types can be now defined at unprecedented resolution using high throughput assays. We analyzed the transcriptional signatures of Drosophila neurons, glia and hemocytes, as ex les of cell types that are related by position (glia/neurons) or function (glia/hemocytes) or that are unrelated (neurons/hemocytes). The most related cells display the highest similarity level (neurons and glia), the least related ones, the lowest (neurons and hemocytes), however, cells can show plastic features. Glia are much more similar to neurons than to hemocytes in the embryo, but are equally similar to the two cell types in the larva, when hemocytes acquire more immune functions. Larval glia and hemocytes display common as well as specific immune features, such as the glia-specific NimA receptor, in agreement with the different environment faced by each cell types. Surprisingly, time represents a key identity parameter, as neurons, hemocytes and glia group more significantly by the stage than by the cell type and larval cells show upregulation of genes involved in chromatin organization and in DNA repair. This latter group of genes is linked to changes in gene expression levels and chromatin organization, revealing a function of these genes beyond DNA repair. Finally, the metabolic profiles reveal cell type-specific signatures and an overall shift from an embryonic, anabolic state to a larval, catabolic state.

The Curse of Conservation: Empirical Evidence Demonstrating That Changes in Land-Use Legislation Drove Catastrophic Bushfires in Southeast Australia

Publisher: MDPI AG

Date: 26-10-2022

DOI: 10.3390/FIRE5060175

Abstract: Protecting “wilderness” and removing human involvement in “nature” was a core pillar of the modern conservation movement through the 20th century. Conservation approaches and legislation informed by this narrative fail to recognise that Aboriginal people have long valued, used, and shaped most landscapes on Earth. Aboriginal people curated open and fire-safe Country for millennia with fire in what are now forested and fire-prone regions. Settler land holders recognised the importance of this and mimicked these practices. The Land Conservation Act of 1970 in Victoria, Australia, prohibited burning by settler land holders in an effort to protect natural landscapes. We present a 120-year record of vegetation and fire regime change from Gunaikurnai Country, southeast Australia. Our data demonstrate that catastrophic bushfires first impacted the local area immediately following the prohibition of settler burning in 1970, which allowed a rapid increase in flammable eucalypts that resulted in the onset of catastrophic bushfires. Our data corroborate local narratives on the root causes of the current bushfire crisis. Perpetuation of the wilderness myth in conservation may worsen this crisis, and it is time to listen to and learn from Indigenous and local people, and to empower these communities to drive research and management agendas.

Vegetation, fire and climate history in central-western Tasmania (41°S), Australia, over the last ∼21,000 years

Publisher: Elsevier BV

Date: 10-2023

DOI: 10.1016/J.QUASCIREV.2023.108315

Revisiting the role of the Gcm transcription factor, from master regulator to Swiss army knife.

Publisher: Informa UK Limited

Date: 03-08-2016

DOI: 10.1080/19336934.2016.1212793

Abstract: Master genes are known to induce the differentiation of a multipotent cell into a specific cell type. These molecules are often transcription factors that switch on the regulatory cascade that triggers cell specification. Gcm was first described as the master gene of the glial fate in Drosophila as it induces the differentiation of neuroblasts into glia in the developing nervous system. Later on, Gcm was also shown to regulate the differentiation of blood, tendon and peritracheal cells as well as that of neuronal subsets. Thus, the glial master gene is used in at least 4 additional systems to promote differentiation. To understand the numerous roles of Gcm, we recently reported a genome-wide screen of Gcm direct targets in the Drosophila embryo. This screen provided new insight into the role and mode of action of this powerful transcription factor, notably on the interactions between Gcm and major differentiation pathways such as the Hedgehog, Notch and JAK/STAT. Here, we discuss the mode of action of Gcm in the different systems, we present new tissues that require Gcm and we revise the concept of 'master gene'.

Transcriptome-wide identification of A > I RNA editing sites by inosine specific cleavage.

Publisher: Cold Spring Harbor Laboratory

Date: 21-12-2013

DOI: 10.1261/RNA.036202.112

Abstract: Adenosine to inosine (A I) RNA editing, which is catalyzed by the ADAR family of proteins, is one of the fundamental mechanisms by which transcriptomic ersity is generated. Indeed, a number of genome-wide analyses have shown that A I editing is not limited to a few mRNAs, as originally thought, but occurs widely across the transcriptome, especially in the brain. Importantly, there is increasing evidence that A I editing is essential for animal development and nervous system function. To more efficiently characterize the complete catalog of ADAR events in the mammalian transcriptome we developed a high-throughput protocol to identify A I editing sites, which exploits the capacity of glyoxal to protect guanosine, but not inosine, from RNAse T1 treatment, thus facilitating extraction of RNA fragments with inosine bases at their termini for high-throughput sequencing. Using this method we identified 665 editing sites in mouse brain RNA, including most known sites and suite of novel sites that include nonsynonymous changes to protein-coding genes, hyperediting of genes known to regulate p53, and alterations to non-protein-coding RNAs. This method is applicable to any biological system for the de novo discovery of A I editing sites, and avoids the complicated informatic and practical issues associated with editing site identification using traditional RNA sequencing data. This approach has the potential to substantially increase our understanding of the extent and function of RNA editing, and thereby to shed light on the role of transcriptional plasticity in evolution, development, and cognition.

Pinstripe: a suite of programs for integrating transcriptomic and proteomic datasets identifies novel proteins and improves differentiation of protein-coding and non-coding genes.

Publisher: Oxford University Press (OUP)

Date: 07-10-2012

DOI: 10.1093/BIOINFORMATICS/BTS582

Abstract: Motivation: Comparing transcriptomic data with proteomic data to identify protein-coding sequences is a long-standing challenge in molecular biology, one that is exacerbated by the increasing size of high-throughput datasets. To address this challenge, and thereby to improve the quality of genome annotation and understanding of genome biology, we have developed an integrated suite of programs, called Pinstripe. We demonstrate its application, utility and discovery power using transcriptomic and proteomic data from publicly available datasets. Results: To demonstrate the efficacy of Pinstripe for large-scale analysis, we applied Pinstripe’s reverse peptide mapping pipeline to a transcript library including de novo assembled transcriptomes from the human Illumina Body Atlas (IBA2) and GENCODE v10 gene annotations, and the EBI Proteomics Identifications Database (PRIDE) peptide database. This analysis identified 736 canonical open reading frames (ORFs) supported by three or more PRIDE peptide fragments that are positioned outside any known coding DNA sequence (CDS). Because of the unfiltered nature of the PRIDE database and high probability of false discovery, we further refined this list using independent evidence for translation, including the presence of a Kozak sequence or functional domains, synonymous/non-synonymous substitution ratios and ORF length. Using this integrative approach, we observed evidence of translation from a previously unknown let7e primary transcript, the archetypical lncRNA H19, and a homolog of RD3. Reciprocally, by exclusion of transcripts with mapped peptides or significant ORFs (& codon), we identify 32 187 loci with RNAs longer than 2000 nt that are unlikely to encode proteins. Availability and implementation: Pinstripe (pinstripe.matticklab.com) is freely available as source code or a Mono binary. Pinstripe is written in C# and runs under the Mono framework on Linux or Mac OS X, and both under Mono and .Net under Windows. Contact: m.dinger@garvan.org.au or j.mattick@garvan.org.au Supplementary information: Supplementary data are available at Bioinformatics online.

Lineage specification in the fly nervous system and evolutionary implications.

Publisher: Informa UK Limited

Date: 09-2013

DOI: 10.4161/CC.25918

Temporal specificity and heterogeneity of Drosophila immune cells

Publisher: EMBO

Date: 03-12-0121

DOI: 10.15252/EMBJ.2020104486

Indigenous knowledge and the shackles of wilderness

Publisher: Proceedings of the National Academy of Sciences

Date: 27-09-2021

DOI: 10.1073/PNAS.2022218118

Abstract: The environmental crises currently gripping the Earth have been codified in a new proposed geological epoch: the Anthropocene. This epoch, according to the Anthropocene Working Group, began in the mid-20th century and reflects the “great acceleration” that began with industrialization in Europe [J. Zalasiewicz et al., Anthropocene 19, 55–60 (2017)]. Ironically, European ideals of protecting a pristine “wilderness,” free from the damaging role of humans, is still often heralded as the antidote to this human-induced crisis [J. E. M. Watson et al., Nature , 563, 27–30 (2018)]. Despite decades of critical engagement by Indigenous and non-Indigenous observers, large international nongovernmental organizations, philanthropists, global institutions, and nation-states continue to uphold the notion of pristine landscapes as wilderness in conservation ideals and practices. In doing so, dominant global conservation policy and public perceptions still fail to recognize that Indigenous and local peoples have long valued, used, and shaped “high-value” bio erse landscapes. Moreover, the exclusion of people from many of these places under the guise of wilderness protection has degraded their ecological condition and is hastening the demise of a number of highly valued systems. Rather than denying Indigenous and local peoples’ agency, access rights, and knowledge in conserving their territories, we draw upon a series of case studies to argue that wilderness is an inappropriate and dehumanizing construct, and that Indigenous and community conservation areas must be legally recognized and supported to enable socially just, empowering, and sustainable conservation across scale.

Université De Lille 3

Location: France

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Institut De Génétique Et De Biologie Moléculaire Et Cellulaire

Location: France

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IMB (University Of Queensland, Australia) / IBMC (Université De Strasbourg, France)

Location: Australia

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University Of Melbourne

Location: Australia

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Linkage Projects - Grant ID: LP220200160

Start Date: 07-2023

End Date: 06-2027

Amount: $476,460.00

Funder: Australian Research Council

Discovery Indigenous - Grant ID: IN170100063

Start Date: 02-2017

End Date: 02-2019

Amount: $372,474.00

Funder: Australian Research Council

Discovery Indigenous - Grant ID: IN140100050

Start Date: 2014

End Date: 12-2016

Amount: $400,000.00

Funder: Australian Research Council

Discovery Indigenous Researchers Development - Grant ID: DI110100019

Start Date: 2011

End Date: 01-2013

Amount: $199,742.00

Funder: Australian Research Council

Discovery Indigenous - Grant ID: IN210100055

Start Date: 05-2021

End Date: 05-2024

Amount: $454,044.00

Funder: Australian Research Council

Discovery Indigenous - Grant ID: IN170100062

Start Date: 09-2017

End Date: 09-2020

Amount: $355,000.00

Funder: Australian Research Council

ARC Centres Of Excellence - Grant ID: CE230100009

Start Date: 07-2024

End Date: 06-2031

Amount: $35,000,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100053

Start Date: 2018

End Date: 12-2018

Amount: $358,031.00

Funder: Australian Research Council