Biology subjects

Todd, C. D.

Publications and source records attributed to Todd, C. D..

5 recordsLinked to original sources

bioRxiv2026

A Cross-kingdom Effector Modulates EDS1-dependent TIR-NLR-mediated Plant Immunity

In the ongoing battle between plants and pathogens, successful pathogens promote colonization by evolving new effectors that manipulate counteractive host responses, such as intracellular nucleotide-binding leucine-rich repeat (NLR)-triggered immunity. Here, we identify a secreted effector, PbSTMI, from the unique intracellular protist Plasmodiophora brassicae, that is conserved across divergent plant pathogens and broadly suppresses ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1)-dependent plant immunity. PbSTMI directly binds EDS1 and promotes its proteasome-mediated degradation, thereby diminishing downstream EDS1 oligomerization required for resistance. PbSTMI overexpression suppresses toll/interleukin-1 receptor (TIR) domain-containing NLR (TIR-NLR)-driven autoimmunity in Arabidopsis and further attenuates salicylic acid-mediated signaling in the autoimmune background. It blocks flg22-induced accumulation of EDS1 and regulates SA-mediated PAMP-triggered immunity (PTI) responses. Oligomerization among PbSTMI and its paralogs suggests coordinated immune suppression during different stages of P. brassicae infection and clubroot disease progression. PbSTMI suppression of EDS1-dependent TIR-NLR-mediated pathways increases susceptibility to a broad range of phytopathogens, including the biotrophs P. brassicae and Erysiphe cichoracearum and the hemibiotrophic Colletotrichum higginsianum. Together, these findings reveal a conserved pathogen strategy that disarms a central immune hub, tipping the balance of the plant-pathogen arms race decisively in favor of the pathogen.

plant biology↗

bioRxiv2025

TurboID-based proximity labeling enables in vivo mapping of Plasmodiophora brassicae secretome in Arabidopsis

O_LIPlasmodiophora brassicae, the causal agent of clubroot disease, is an obligate biotrophic protist belonging to the poorly characterized Rhizaria. Its intracellular lifestyle and resistance to genetic manipulation have hindered functional analysis of its effector repertoire, leaving mechanisms underlying disease development unresolved. Here, we sought to experimentally define the P. brassicae secretome within infected plant cells and identify effectors targeted to specific host subcellular compartments. C_LIO_LIA proximity labeling approach based on the TurboID biotin ligase was used to capture pathogen-derived proteins within the nucleus, cytosol, endoplasmic reticulum, and plasma membrane of infected Arabidopsis roots during primary and secondary stages of clubroot disease. C_LIO_LIThis strategy yielded the first in planta experimental view of the P. brassicae secretome, identifying both established and previously uncharacterized effectors. The resulting dataset provides a valuable resource and methodological framework for dissecting effector function in this and other intracellular plant pathogens. C_LIO_LIThis study expands our understanding of Rhizarian pathogenicity and provides a methodological template for identifying the secretomes of other obligatory intracellular plant pathogens. C_LI

plant biology↗

bioRxiv2024

Epigenetic priming of embryonic enhancer elements coordinates developmental gene networks

Embryonic development requires the accurate spatiotemporal execution of cell lineage-specific gene expression programs, which are controlled by transcriptional enhancers. Developmental enhancers adopt a primed chromatin state prior to their activation; however how this primed enhancer state is established, maintained, and how it affects the regulation of developmental gene networks remains poorly understood. Here, we use comparative multi-omic analyses of human and mouse early embryonic development to identify subsets of post-gastrulation lineage-specific enhancers which are epigenetically primed ahead of their activation, marked by the histone modification H3K4me1 within the epiblast. We show that epigenetic priming occurs at lineage-specific enhancers for all three germ layers, and that epigenetic priming of enhancers confers lineage-specific regulation of key developmental gene networks. Surprisingly in some cases, lineage-specific enhancers are epigenetically marked already in the zygote, weeks before their activation during lineage specification. Moreover, we outline a generalisable strategy to use naturally occurring human genetic variation to delineate important sequence determinants of primed enhancer function. Our findings identify an evolutionarily conserved program of enhancer priming and begin to dissect the temporal dynamics and mechanisms of its establishment and maintenance during early mammalian development.

developmental biology↗

bioRxiv2019

Endogenous retroviruses are a source of oncogenic enhancers in acute myeloid leukemia

Acute myeloid leukemia (AML) is a highly aggressive hematopoietic malignancy, defined by a series of genetic and epigenetic alterations, which result in deregulation of transcriptional networks. One understudied but important source of transcriptional regulators are transposable elements (TEs), which are widespread throughout the human genome. Aberrant usage of these sequences could therefore contribute to oncogenic transcriptional circuits. However, the regulatory influence of TEs and their links to disease pathogenesis remain unexplored in AML. Using epigenomic data from AML primary samples and leukemia cell lines, we identified six endogenous retrovirus (ERV) families with AML-associated enhancer chromatin signatures that are enriched in binding of key regulators of hematopoiesis and AML pathogenesis. Using both CRISPR-mediated locus-specific genetic editing and simultaneous epigenetic silencing of multiple ERVs, we demonstrate that ERV deregulation directly alters the expression of adjacent genes in AML. Strikingly, deletion or epigenetic silencing of an ERV-derived enhancer suppressed cell growth by inducing apoptosis in leukemia cell lines. Our work reveals that ERVs are a previously unappreciated source of AML enhancers that have the potential to play key roles in leukemogenesis. We suggest that ERV activation provides an additional layer of gene regulation in AML that may be exploited by cancer cells to help drive tumour heterogeneity and evolution.

genetics↗

bioRxiv2018

Functional evaluation of transposable elements as transcriptional enhancers in mouse embryonic and trophoblast stem cells

The recurrent invasion and expansion of transposable elements (TEs) throughout evolution brought with it a vast array of coding and non-coding sequences that can serve as substrates for natural selection. Namely, TEs are thought to have contributed to the establishment of gene regulatory networks via their cis-acting elements. Both the embryonic and extraembryonic lineages of the early mouse embryo are thought to have benefited from the co-option of TEs as distal enhancer elements. However, there is little to no evidence that these particular TEs play significant roles in the regulation of gene expression. Here we tested for roles of TEs as enhancers in mouse embryonic and trophoblast stem cells by combining bioinformatic analyses with genetic and epigenetic editing experiments. Epigenomic and transcriptomic data from wildtype cells suggested that a large number of TEs played a role in the establishment of highly tissue-specific gene expression programmes. Through genetic editing of individual TEs we confirmed a subset of these regulatory relationships. However, a wider survey via CRISPR interference of RLTR13D6 elements in embryonic stem cells revealed that only a minority play significant roles in gene regulation. Our results suggest that a small proportion of TEs contribute to the mouse pluripotency regulatory network, and highlight the importance of functional experiments when evaluating the role of TEs in gene regulation.

genetics↗