Publications

2024
Singh N, Rolandelli A, O'Neal AJ, Butler LR, Samaddar S, Loukaitis-Yousey HJ, et al. Genetic manipulation of an Ixodes scapularis cell line. mBio. 2024;Feb (21) :e0247923. Abstract
Although genetic manipulation is one of the hallmarks of model organisms, its applicability to non-model species has remained difficult due to our limited understanding of their fundamental biology. For instance, manipulation of a cell line originated from the black-legged tick Ixodes scapularis, an arthropod that serves as a vector for several human pathogens, has yet to be established. Here, we demonstrate the successful genetic modification of the commonly used tick ISE6 line through ectopic expression and clustered regularly interspaced palindromic repeats [(CRISPR)/CRISPR-associated protein 9 (Cas9)] genome editing. We performed ectopic expression using nucleofection and attained CRISPR-Cas9 editing via homology-dependent recombination. Targeting the E3 ubiquitin ligase x-linked inhibitor of apoptosis (xiap) and its substrate p47 led to an alteration in molecular signaling within the immune deficiency network and increased infection of the rickettsial agent Anaplasma phagocytophilum in I. scapularis ISE6 cells. Collectively, our findings complement techniques for the genetic engineering of I. scapularis ticks, which currently limit efficient and scalable molecular genetic screens in vivo.IMPORTANCEGenetic engineering in arachnids has lagged compared to insects, largely because of substantial differences in their biology. This study unveils the implementation of ectopic expression and CRISPR-Cas9 gene editing in a tick cell line. We introduced fluorescently tagged proteins in ISE6 cells and edited its genome via homology-dependent recombination. We ablated the expression of xiap and p47, two signaling molecules present in the immune deficiency (IMD) pathway of Ixodes scapularis. Impairment of the tick IMD pathway, an analogous network of the tumor necrosis factor receptor in mammals, led to enhanced infection of the rickettsial agent Anaplasma phagocytophilum. Altogether, our findings provide a critical technical resource to the scientific community to enable a deeper understanding of biological circuits in the black-legged tick I. scapularis.
singh-et-al-2024-genetic-manipulation-of-an-ixodes-scapularis-cell-line.pdf
Xu J, Liu Y, Yang F, Cao Y, Chen W, Li JSS, et al. Mechanistic characterization of a Drosophila model of paraneoplastic nephrotic syndrome. Nature Communications. 2024;Feb 9 (15(1) :1241. Abstract
Paraneoplastic syndromes occur in cancer patients and originate from dysfunction of organs at a distance from the tumor or its metastasis. A wide range of organs can be affected in paraneoplastic syndromes; however, the pathological mechanisms by which tumors influence host organs are poorly understood. Recent studies in the fly uncovered that tumor secreted factors target host organs, leading to pathological effects. In this study, using a Drosophila gut tumor model, we characterize a mechanism of tumor-induced kidney dysfunction. Specifically, we find that Pvf1, a PDGF/VEGF signaling ligand, secreted by gut tumors activates the PvR/JNK/Jra signaling pathway in the principal cells of the kidney, leading to mis-expression of renal genes and paraneoplastic renal syndrome-like phenotypes. Our study describes an important mechanism by which gut tumors perturb the function of the kidney, which might be of clinical relevance for the treatment of paraneoplastic syndromes.
41467_2024_article_45493.pdf
Kang J, Zhang C, Wang Y, Peng J, Berger B, Perrimon N, et al. Lipophorin receptors genetically modulate neurodegeneration caused by reduction of Psn expression in the aging Drosophila brain. Genetics. 2024;226 (1) :iyad202. Abstract
Mutations in the Presenilin (PSEN) genes are the most common cause of early-onset familial Alzheimer's disease (FAD). Studies in cell culture, in vitro biochemical systems, and knockin mice showed that PSEN mutations are loss-of-function mutations, impairing γ-secretase activity. Mouse genetic analysis highlighted the importance of Presenilin (PS) in learning and memory, synaptic plasticity and neurotransmitter release, and neuronal survival, and Drosophila studies further demonstrated an evolutionarily conserved role of PS in neuronal survival during aging. However, molecular pathways that interact with PS in neuronal survival remain unclear. To identify genetic modifiers that modulate PS-dependent neuronal survival, we developed a new DrosophilaPsn model that exhibits age-dependent neurodegeneration and increases of apoptosis. Following a bioinformatic analysis, we tested top ranked candidate genes by selective knockdown (KD) of each gene in neurons using two independent RNAi lines in Psn KD models. Interestingly, 4 of the 9 genes enhancing neurodegeneration in Psn KD flies are involved in lipid transport and metabolism. Specifically, neuron-specific KD of lipophorin receptors, lpr1 and lpr2, dramatically worsens neurodegeneration in Psn KD flies, and overexpression of lpr1 or lpr2 does not alleviate Psn KD-induced neurodegeneration. Furthermore, lpr1 or lpr2 KD alone also leads to neurodegeneration, increased apoptosis, climbing defects, and shortened lifespan. Lastly, heterozygotic deletions of lpr1 and lpr2 or homozygotic deletions of lpr1 or lpr2 similarly lead to age-dependent neurodegeneration and further exacerbate neurodegeneration in Psn KD flies. These findings show that LpRs modulate Psn-dependent neuronal survival and are critically important for neuronal integrity in the aging brain.
lipophorin_receptors_genetically_modulate_neurodegeneration_caused_by_reduction_of_psn_expression_in_the_aging_drosophila_brain.pdf
2023
Song S, Cho B, Weiner A, Nissen SB, Naharros IO, Bosch PS, et al. Protein phosphatase 1 regulates core PCP signaling. EMBO Reports. 2023;Nov (17) :e56997. Abstract
Planar cell polarity (PCP) signaling polarizes epithelial cells within the plane of an epithelium. Core PCP signaling components adopt asymmetric subcellular localizations within cells to both polarize and coordinate polarity between cells. Achieving subcellular asymmetry requires additional effectors, including some mediating post-translational modifications of core components. Identification of such proteins is challenging due to pleiotropy. We used mass spectrometry-based proximity labeling proteomics to identify such regulators in the Drosophila wing. We identified the catalytic subunit of protein phosphatase1, Pp1-87B, and show that it regulates core protein polarization. Pp1-87B interacts with the core protein Van Gogh and at least one serine/threonine kinase, Dco/CKIε, that is known to regulate PCP. Pp1-87B modulates Van Gogh subcellular localization and directs its dephosphorylation in vivo. PNUTS, a Pp1 regulatory subunit, also modulates PCP. While the direct substrate(s) of Pp1-87B in control of PCP is not known, our data support the model that cycling between phosphorylated and unphosphorylated forms of one or more core PCP components may regulate acquisition of asymmetry. Finally, our screen serves as a resource for identifying additional regulators of PCP signaling.
protein_phosphatase_1_regulates_core_pcp_signaling.pdf
Mohr S, Kim A-R, Hu Y, Perrimon N. Finding information about uncharacterized Drosophila melanogaster genes. Genetics. 2023;10.1093/genetics/iyad187. iyad187.pdf
Bosch J, Keith N, Escobedo F, Fisher WF, LaGraff JT, Rabasco J, et al. Molecular and functional characterization of the Drosophila melanogaster conserved smORFeome. Cell Reports. 2023;42 (113311) :doi: 10.1016/j.celrep.2023.113311. PMID: 37889754. Abstract
Short polypeptides encoded by small open reading frames (smORFs) are ubiquitously found in eukaryotic genomes and are important regulators of physiology, development, and mitochondrial processes. Here, we focus on a subset of 298 smORFs that are evolutionarily conserved between Drosophila melanogaster and humans. Many of these smORFs are conserved broadly in the bilaterian lineage, and ∼182 are conserved in plants. We observe remarkably heterogeneous spatial and temporal expression patterns of smORF transcripts-indicating wide-spread tissue-specific and stage-specific mitochondrial architectures. In addition, an analysis of annotated functional domains reveals a predicted enrichment of smORF polypeptides localizing to mitochondria. We conduct an embryonic ribosome profiling experiment and find support for translation of 137 of these smORFs during embryogenesis. We further embark on functional characterization using CRISPR knockout/activation, RNAi knockdown, and cDNA overexpression, revealing diverse phenotypes. This study underscores the importance of identifying smORF function in disease and phenotypic diversity.
molecular_and_functional_characterization_of_the_drosophila_melanogaster_conserved_smorfome.pdf
Sun X, Shen J, Perrimon N, Kong X, Wang D. The endoribonuclease Arlr is required to maintain lipid homeostasis by downregulating lipolytic genes during aging. Nature Communications. 2023;14 (6254). s41467-023-42042-7.pdf
Petsakou A, Liu Y, Liu Y, Comjean A, Hu Y, Perrimon N. Cholinergic neurons trigger epithelial Ca2+ currents to heal the gut. Nature. 2023;Sep 18 :doi: 10.1038/s41586-023-06627-y. Abstract
A fundamental and unresolved question in regenerative biology is how tissues return to homeostasis after injury. Answering this question is essential for understanding the etiology of chronic disorders such as inflammatory bowel diseases and cancer1. We used the Drosophila midgut2 to investigate this and discovered that during regeneration a subpopulation of cholinergic3 neurons triggers Ca2+ currents among intestinal epithelial cells, the enterocytes, to promote return to homeostasis. We found that down-regulation of the conserved cholinergic enzyme Acetylcholinesterase4 in the gut epithelium enables acetylcholine from specific TNF/Egr5-sensing cholinergic neurons to activate nicotinic receptors in innervated enterocytes. This activation triggers high Ca2+ that spreads in the epithelium through Inx2/Inx7 gap junctions6, promoting enterocyte maturation followed by reduction of proliferation and inflammation. Disrupting this process causes chronic injury consisting of ion imbalance, Yki/Yap activation7, cell death and increase of inflammatory cytokines reminiscent of inflammatory bowel diseases8. Altogether, the conserved cholinergic pathway facilitates epithelial Ca2+ currents that heal the intestinal epithelium. Our findings demonstrate nerve- and bioelectric9-dependent intestinal regeneration and advance our current understanding of how a tissue returns to homeostasis after injury.
cholinergic_neurons_trigger_epithelial_ca2_currents_to_heal_the_gut.pdf
Saavedra P, Dumesic PA, Hu Y, Filine E, Jouandin P, Binari R, et al. REPTOR and CREBRF encode key regulators of muscle energy metabolism. Nature Communications. 2023;Aug 15 (14(1) :4943. Abstract
Metabolic flexibility of muscle tissue describes the adaptive capacity to use different energy substrates according to their availability. The disruption of this ability associates with metabolic disease. Here, using a Drosophila model of systemic metabolic dysfunction triggered by yorkie-induced gut tumors, we show that the transcription factor REPTOR is an important regulator of energy metabolism in muscles. We present evidence that REPTOR is activated in muscles of adult flies with gut yorkie-tumors, where it modulates glucose metabolism. Further, in vivo studies indicate that sustained activity of REPTOR is sufficient in wildtype muscles to repress glycolysis and increase tricarboxylic acid (TCA) cycle metabolites. Consistent with the fly studies, higher levels of CREBRF, the mammalian ortholog of REPTOR, reduce glycolysis in mouse myotubes while promoting oxidative metabolism. Altogether, our results define a conserved function for REPTOR and CREBRF as key regulators of muscle energy metabolism.
reptor_and_crebrf_encode_key_regulators_of_muscle_energy_metabolism.pdf
Coleman-Gosser N, Raghuvansh S, Stitzinger S, Hu T, Chen W, Luhur A, et al. Continuous muscle, glial, epithelial, neuronal, and hemocyte cell lines for Drosophila research. Elife. 2023;Jul 20 (12) :e85814. Abstract
Expression of activated Ras, RasV12, provides Drosophila cultured cells with a proliferation and survival advantage that simplifies the generation of continuous cell lines. Here, we used lineage-restricted RasV12 expression to generate continuous cell lines of muscle, glial, and epithelial cell type. Additionally, cell lines with neuronal and hemocyte characteristics were isolated by cloning from cell cultures established with broad RasV12 expression. Differentiation with the hormone ecdysone caused maturation of cells from mesoderm lines into active muscle tissue and enhanced dendritic features in neuronal-like lines. Transcriptome analysis showed expression of key cell-type-specific genes and the expected alignment with single-cell sequencing and in situ data. Overall, the technique has produced in vitro cell models with characteristics of glia, epithelium, muscle, nerve, and hemocyte. The cells and associated data are available from the Drosophila Genomic Resource Center.
elife-85814.pdf
Li Y, Zhou X, Ding G, Zhao P, Tan K, Cheng L, et al. Gut AstA mediates sleep deprivation-induced energy wasting in Drosophila. Cell Discovery. 2023;9 (1) :49. Abstract
Severe sleep deprivation (SD) has been highly associated with systemic energy wasting, such as lipid loss and glycogen depletion. Despite immune dysregulation and neurotoxicity observed in SD animals, whether and how the gut-secreted hormones participate in SD-induced disruption of energy homeostasis remains largely unknown. Using Drosophila as a conserved model organism, we characterize that production of intestinal Allatostatin A (AstA), a major gut-peptide hormone, is robustly increased in adult flies bearing severe SD. Interestingly, the removal of AstA production in the gut using specific drivers significantly improves lipid loss and glycogen depletion in SD flies without affecting sleep homeostasis. We reveal the molecular mechanisms whereby gut AstA promotes the release of an adipokinetic hormone (Akh), an insulin counter-regulatory hormone functionally equivalent to mammalian glucagon, to mobilize systemic energy reserves by remotely targeting its receptor AstA-R2 in Akh-producing cells. Similar regulation of glucagon secretion and energy wasting by AstA/galanin is also observed in SD mice. Further, integrating single-cell RNA sequencing and genetic validation, we uncover that severe SD results in ROS accumulation in the gut to augment AstA production via TrpA1. Altogether, our results demonstrate the essential roles of the gut-peptide hormone AstA in mediating SD-associated energy wasting.
gut_asta_mediates_sleep_deprivation-induced_energy_wasting_in_drosophila.pdf
Ewen-Campen B, Luan H, Xu J, Singh R, Joshi N, Thakkar T, et al. split-intein Gal4 provides intersectional genetic labeling that is repressible by Gal80. PNAS. 2023;120 (24) :e2304730120. Abstract
The  split-Gal4  system  allows  for  intersectional  genetic  labeling  of  highly  specific  cell types and tissues in Drosophila. However, the existing split-Gal4 system, unlike the  standard  Gal4  system,  cannot  be  repressed  by  Gal80,  and  therefore  cannot  be  controlled temporally. This lack of temporal control precludes split-Gal4 experiments in  which  a  genetic  manipulation  must  be  restricted  to  specific  timepoints.  Here,  we  describe  a  split-Gal4  system  based  on  a  self-excising  split-intein,  which  drives  transgene expression as strongly as the current split-Gal4 system and Gal4 reagents, yet which is repressible by Gal80. We demonstrate the potent inducibility of “split-intein Gal4” in vivo using both fluorescent reporters and via reversible tumor induction in the gut. Further, we show that our split-intein Gal4 can be extended to the drug-inducible GeneSwitch  system,  providing  an  independent  method  for  intersectional  labeling  with inducible control. We also show that the split-intein Gal4 system can be used to  generate  highly  cell  type–specific  genetic  drivers  based  on  in  silico  predictions  generated by single-cell RNAseq (scRNAseq) datasets, and we describe an algorithm (“Two  Against  Background”  or  TAB)  to  predict  cluster-specific  gene  pairs  across  multiple tissue-specific scRNA datasets. We provide a plasmid toolkit to efficiently create  split-intein  Gal4  drivers  based  on  either  CRISPR  knock-ins  to  target  genes  or using enhancer fragments. Altogether, the split-intein Gal4 system allows for the creation of highly specific intersectional genetic drivers that are inducible/repressible.
pnas.2304730120.pdf
Xu C, Xu J, Tang H-W, Ericsson M, Weng J-H, DiRusso J, et al. A phosphate-sensing organelle regulates phosphate and tissue homeostasis. Nature. 2023;May 3 :doi: 10.1038/s41586-023-06039-y. Abstract
Inorganic phosphate (Pi) is one of the essential molecules for life. However, little is known about intracellular Pi metabolism and signalling in animal tissues1. Following the observation that chronic Pi starvation causes hyperproliferation in the digestive epithelium of Drosophila melanogaster, we determined that Pi starvation triggers the downregulation of the Pi transporter PXo. In line with Pi starvation, PXo deficiency caused midgut hyperproliferation. Interestingly, immunostaining and ultrastructural analyses showed that PXo specifically marks non-canonical multilamellar organelles (PXo bodies). Further, by Pi imaging with a Förster resonance energy transfer (FRET)-based Pi sensor2, we found that PXo restricts cytosolic Pi levels. PXo bodies require PXo for biogenesis and undergo degradation following Pi starvation. Proteomic and lipidomic characterization of PXo bodies unveiled their distinct feature as an intracellular Pi reserve. Therefore, Pi starvation triggers PXo downregulation and PXo body degradation as a compensatory mechanism to increase cytosolic Pi. Finally, we identified connector of kinase to AP-1 (Cka), a component of the STRIPAK complex and JNK signalling3, as the mediator of PXo knockdown- or Pi starvation-induced hyperproliferation. Altogether, our study uncovers PXo bodies as a critical regulator of cytosolic Pi levels and identifies a Pi-dependent PXo-Cka-JNK signalling cascade controlling tissue homeostasis.
s41586-023-06039-y_1.pdf
Ferrer M, et al. Cachexia: A systemic consequence of progressive, unresolved disease. Cell. 2023;Apr 27;186 (9) :1824-1845. doi: 10.1016/j.cell.2023.03.028. Abstract

Cachexia, a systemic wasting condition, is considered a late consequence of diseases, including cancer, organ failure, or infections, and contributes to significant morbidity and mortality. The induction process and mechanistic progression of cachexia are incompletely understood. Refocusing academic efforts away from advanced cachexia to the etiology of cachexia may enable discoveries of new therapeutic approaches. Here, we review drivers, mechanisms, organismal predispositions, evidence for multi-organ interaction, model systems, clinical research, trials, and care provision from early onset to late cachexia. Evidence is emerging that distinct inflammatory, metabolic, and neuro-modulatory drivers can initiate processes that ultimately converge on advanced cachexia.

 

cachexia_a_systemic_consequence_of_progressive_unresolved_disease_elsevier_enhanced_reader.pdf
Chung H-L, Ye Q, ye-Jin Park, Zuo Z, Mok J-W, Kanca O, et al. Very-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation. Cell Metabolism. 2023;May 2;35 (5) :855-874.e5. doi: 10.1016/j.cmet.2023.03.022. Epub 2023 Apr 20. Abstract
VLCFAs (very-long-chain fatty acids) are the most abundant fatty acids in myelin. Hence, during demyelination or aging, glia are exposed to higher levels of VLCFA than normal. We report that glia convert these VLCFA into sphingosine-1-phosphate (S1P) via a glial-specific S1P pathway. Excess S1P causes neuroinflammation, NF-κB activation, and macrophage infiltration into the CNS. Suppressing the function of S1P in fly glia or neurons, or administration of Fingolimod, an S1P receptor antagonist, strongly attenuates the phenotypes caused by excess VLCFAs. In contrast, elevating the VLCFA levels in glia and immune cells exacerbates these phenotypes. Elevated VLCFA and S1P are also toxic in vertebrates based on a mouse model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). Indeed, reducing VLCFA with bezafibrate ameliorates the phenotypes. Moreover, simultaneous use of bezafibrate and fingolimod synergizes to improve EAE, suggesting that lowering VLCFA and S1P is a treatment avenue for MS.
1-s2.0-s1550413123001274-main.pdf
Xia B, Viswanatha R, Hu Y, Mohr S, Perrimon N. Pooled genome-wide CRISPR activation screening for rapamycin resistance genes in Drosophila cells. Elife. 2023;Apr 20 (12) :e85542. doi: 10.7554/eLife.85542. Abstract
Loss-of-function and gain-of-function genetic perturbations provide valuable insights into gene function. In Drosophila cells, while genome-wide loss-of-function screens have been extensively used to reveal mechanisms of a variety of biological processes, approaches for performing genome-wide gain-of-function screens are still lacking. Here, we describe a pooled CRISPR activation (CRISPRa) screening platform in Drosophila cells and apply this method to both focused and genome-wide screens to identify rapamycin resistance genes. The screens identified three genes as novel rapamycin resistance genes: a member of the SLC16 family of monocarboxylate transporters (CG8468), a member of the lipocalin protein family (CG5399), and a zinc finger C2H2 transcription factor (CG9932). Mechanistically, we demonstrate that CG5399 overexpression activates the RTK-Akt-mTOR signaling pathway and that activation of insulin receptor (InR) by CG5399 requires cholesterol and clathrin-coated pits at the cell membrane. This study establishes a novel platform for functional genetic studies in Drosophila cells.
elife-85542.pdf
Tang H-W, et al. Next-generation large-scale binary protein interaction network for Drosophila melanogaster. Nature Communications. 2023;Apr 15;14 (1) :2162. doi: 10.1038/s41467-023-37876-0. Abstract
Generating reference maps of interactome networks illuminates genetic studies by providing a protein-centric approach to finding new components of existing pathways, complexes, and processes. We apply state-of-the-art methods to identify binary protein-protein interactions (PPIs) for Drosophila melanogaster. Four all-by-all yeast two-hybrid (Y2H) screens of > 10,000 Drosophila proteins result in the 'FlyBi' dataset of 8723 PPIs among 2939 proteins. Testing subsets of data from FlyBi and previous PPI studies using an orthogonal assay allows for normalization of data quality; subsequent integration of FlyBi and previous data results in an expanded binary Drosophila reference interaction network, DroRI, comprising 17,232 interactions among 6511 proteins. We use FlyBi data to generate an autophagy network, then validate in vivo using autophagy-related assays. The deformed wings (dwg) gene encodes a protein that is both a regulator and a target of autophagy. Altogether, these resources provide a foundation for building new hypotheses regarding protein networks and function.
next-generation_large-scale_binary_protein_interaction_network_for_drosophila_melanogaster.pdf
Al-Sawaf O, et al. Body composition and lung cancer-associated cachexia in TRACERx. Nature Medicine. 2023;Apr;29 (4) :846-858 doi: 10.1038/s41591-023-02232-8. Abstract
Cancer-associated cachexia (CAC) is a major determinant of morbidity and mortality in patients with non-small cell lung cancer (NSCLC). Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate possible biological processes and mediators that contribute to the development of CAC. Computed tomography-based (CT) body composition analysis of 651 patients in TRACERx suggested that patients with low skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, represented by the bottom 20th percentile, had significantly shorter lung cancer-specific survival (LCSS) and overall survival (OS). This finding was validated in 420 patients in the independent Boston Lung Cancer Study. In a longitudinal subset of 272 patients in TRACERx who experienced disease relapse, loss of adipose tissue, skeletal muscle, or body weight in the interval between diagnosis and relapse, was significantly associated with shorter LCSS and OS. Patients with one or more features encompassing loss of adipose or muscle tissue, or BMI-adjusted weight loss according to specific thresholds were classified as having developed CAC and were found to have distinct tumour genomic and transcriptomic profiles compared with patients who did not develop such features at relapse. Primary NSCLCs from patients in the CAC group were characterised by enrichment of inflammatory signalling and epithelial-mesenchymal transitional pathways, and differentially expressed genes upregulated in these tumours included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory analysis of putative circulating cachexia mediators performed in a subset of 256 baseline and relapse plasma samples from TRACERx, proteomic analysis revealed a significant association between circulating GDF15 and loss of body weight, skeletal muscle, and adipose tissue at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC.
body_composition_and_lung_cancer-associated_cachexia_in_tracerx.pdf
Hu Y, Comjean A, Attrill H, Antonazzo G, Thurmond J, Fangge L, et al. PANGEA: A New Gene Set Enrichment Tool for Drosophila and Common Research Organisms. Nucleic Acids Research. 2023;May 1 (gkad331) :doi: 10.1093/nar/gkad331. Abstract
Gene set enrichment analysis (GSEA) plays an important role in large-scale data analysis, helping scientists discover the underlying biological patterns over-represented in a gene list resulting from, for example, an 'omics' study. Gene Ontology (GO) annotation is the most frequently used classification mechanism for gene set definition. Here we present a new GSEA tool, PANGEA (PAthway, Network and Gene-set Enrichment Analysis; https://www.flyrnai.org/tools/pangea/ ), developed to allow a more flexible and configurable approach to data analysis using a variety of classification sets. PANGEA allows GO analysis to be performed on different sets of GO annotations, for example excluding high-throughput studies. Beyond GO, gene sets for pathway annotation and protein complex data from various resources as well as expression and disease annotation from the Alliance of Genome Resources (Alliance). In addition, visualisations of results are enhanced by providing an option to view network of gene set to gene relationships. The tool also allows comparison of multiple input gene lists and accompanying visualisation tools for quick and easy comparison. This new tool will facilitate GSEA for Drosophila and other major model organisms based on high-quality annotated information available for these species.
gkad331.pdf
He L, Norbert P. Synthetic Notch receptors and their applications to study cell-cell contacts in vivo. Developmental Cell. 2023;58 (3) :171-173. Abstract
Physical cell-cell interaction is a fundamental mechanism that controls the development and physiology of multicellular organisms. However, methods to study cell contact within complex tissues are limited. In a recent issue of Science, Zhang et al. developed synthetic Notch (synNotch)-based tools that can monitor and trace cell-cell contacts in mammals.
synthetic_notch_receptors_and_their_applications_to_study_cell-cell_contacts_innbspvivo.pdf

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