Alexander M. van der Linden

ORCID: 0000-0002-4870-7684
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About
Contact & Profiles
Research Areas
  • Genetics, Aging, and Longevity in Model Organisms
  • Circadian rhythm and melatonin
  • MicroRNA in disease regulation
  • Circular RNAs in diseases
  • Neurobiology and Insect Physiology Research
  • RNA Research and Splicing
  • Adipose Tissue and Metabolism
  • CRISPR and Genetic Engineering
  • GDF15 and Related Biomarkers
  • Genomics, phytochemicals, and oxidative stress
  • Light effects on plants
  • Birth, Development, and Health
  • Chromosomal and Genetic Variations
  • Histone Deacetylase Inhibitors Research
  • Spaceflight effects on biology
  • Ubiquitin and proteasome pathways
  • Protein Hydrolysis and Bioactive Peptides
  • Genetics and Neurodevelopmental Disorders
  • Neuroinflammation and Neurodegeneration Mechanisms
  • Receptor Mechanisms and Signaling
  • Mitochondrial Function and Pathology
  • Neurogenesis and neuroplasticity mechanisms
  • Tryptophan and brain disorders
  • Sleep and Wakefulness Research
  • Pluripotent Stem Cells Research

University of Nevada, Reno
2015-2025

Brandeis University
2006-2010

Hubrecht Institute for Developmental Biology and Stem Cell Research
2001-2006

RNA-mediated interference (RNAi) is a method to inhibit gene function by introduction of double-stranded RNA (dsRNA). Recently, an RNAi library was constructed that consists bacterial clones expressing dsRNA, corresponding nearly 90% the 19,427 predicted genes C. elegans. Feeding this standard wild-type laboratory strain Bristol N2 detected phenotypes for approximately 10% genes. To increase number which loss-of-function phenotype can be detected, we undertook genome-wide screen using rrf-3...

10.1371/journal.pbio.0000012 article EN cc-by PLoS Biology 2003-10-12

Circular RNAs (circRNAs) are non-coding mostly derived from exons of protein-coding genes via a back-splicing process. The expression hundreds circRNAs accumulates during healthy aging and is associated with Alzheimer’s disease (AD), which characterized by the accumulation amyloid-beta (Aβ) proteins. In C. elegans , many were previously found to accumulate aging, loss age-accumulated CREB gene (circ- crh-1 ) increase mean lifespan. Here, we used study effects on age-related onset...

10.3389/fnagi.2025.1464015 article EN cc-by Frontiers in Aging Neuroscience 2025-03-24

Circular RNAs (CircRNAs) are a newly appreciated class of that lack free 5′ and 3′ ends, expressed by the thousands in diverse forms life, mostly enigmatic function. Ostensibly due to their resistance exonucleases, circRNAs known be exceptionally stable. Previous work Drosophila mice have shown increase during aging neural tissues. Here, we examined global profile C. elegans performing ribo-depleted total RNA-seq from fourth larval stage (L4) through 10-day old adults. Using stringent...

10.1186/s12864-017-4386-y article EN cc-by BMC Genomics 2018-01-03

Many lines of evidence point to links between sleep regulation and energy homeostasis, but mechanisms underlying these connections are unknown. During Caenorhabditis elegans sleep, energetic stores allocated nonneural tasks with a resultant drop in the overall fat charge. Mutants lacking KIN-29, C. homolog mammalian Salt-Inducible Kinase (SIK) that signals pressure, have low ATP levels despite high-fat stores, indicating defective response cellular deficits. Liberating corrects adiposity...

10.1371/journal.pbio.3000220 article EN cc-by PLoS Biology 2020-04-21

Most organisms have an endogenous circadian clock that is synchronized to environmental signals such as light and temperature. Although rhythms been described in the nematode Caenorhabditis elegans at behavioral level, these appear be relatively non-robust. Moreover, contrast other animal models, no transcriptional identified. Thus, whether this organism contains a bona fide remains open question. Here we use genome-wide expression profiling experiments identify light- temperature-entrained...

10.1371/journal.pbio.1000503 article EN cc-by PLoS Biology 2010-10-12

Abstract Background The left and right AWC olfactory neurons in Caenorhabditis elegans differ their functions expression of chemosensory receptor genes; each animal, one randomly takes on identity, designated OFF , the contralateral becomes ON . Signaling between induces left-right asymmetry through a gap junction network claudin-related protein, which inhibit calcium-regulated MAP kinase pathway neuron that Results We show here gene olrn-1 acts downstream claudin genes to calcium-MAP...

10.1186/1749-8104-2-24 article EN cc-by Neural Development 2007-11-06

Feeding state and food availability can dramatically alter an animals' sensory response to chemicals in its environment. Dynamic changes the expression of chemoreceptor genes may underlie some these state-dependent chemosensory behavior, but mechanisms underlying are unknown. Here, we identified a KIN-29 (SIK)-dependent chemoreceptor, srh-234, C. elegans whose ADL neuron type is regulated by integration internal feeding signals. We show that addition KIN-29, signaling mediated DAF-2...

10.1371/journal.pgen.1004707 article EN cc-by PLoS Genetics 2014-10-30

Abstract The regulation of chemoreceptor (CR) gene expression by environmental signals and internal cues may contribute to the modulation multiple physiological processes behavior in Caenorhabditis elegans. We previously showed that KIN-29, a homolog salt-inducible kinase, acts sensory neurons regulate subset CR genes, as well behaviors. Here we show cGMP-dependent protein kinase EGL-4 partly parallel with KIN-29 expression. Sensory inputs inhibit both functions, function is inhibited turn...

10.1534/genetics.108.094771 article EN Genetics 2008-10-03

The genome of Caenorhabditis elegans harbors two genes for G-protein beta-subunits. Here, we describe the characterization second beta-subunit gene gpb-2. In contrast to gpb-1, gpb-2 is not an essential even though, like expressed during development, in nervous system, and muscle cells. A loss-of-function mutation produces a variety behavioral defects, including delayed egg laying reduced pharyngeal pumping. Genetic analysis shows that GPB-2 interacts with GOA-1 (homologue mammalian...

10.1093/genetics/158.1.221 article EN Genetics 2001-05-01

Abstract There is significant and often heritable variation in cognition its underlying neural mechanisms, yet specific genetic contributions to such are not well characterized. Black‐capped chickadees present a good model investigate the basis of because they exhibit tremendous climate‐related memory, hippocampal morphology neurogenesis rates throughout North American continent, these cognitive traits appear have basis. We examined transcriptome profiles laboratory‐reared from two most...

10.1111/mec.12146 article EN Molecular Ecology 2012-12-03

Food and feeding-state dependent changes in chemoreceptor gene expression may allow Caenorhabditis elegans to modify their chemosensory behavior, but the mechanisms essential for these remain poorly characterized. We had previously shown that of a feeding state-dependent gene, srh-234, ADL sensory neuron C. is regulated via MEF-2 transcription factor. Here, we show acts together with basic helix-loop-helix (bHLH) factors regulate srh-234 as function state. identify cis-regulatory MEF2...

10.1371/journal.pgen.1006237 article EN cc-by PLoS Genetics 2016-08-03

Abstract Accumulation of circular RNAs (circRNAs) during aging occurs on a genome‐wide level for multiple organisms, but its significance is unknown. Generating circRNA loss‐of‐function mutants difficult because the vast majority these are comprised exons shared with protein‐coding mRNAs. In Caenorhabditis elegans , most circRNAs were previously found to accumulate aging. Two abundant, age‐accumulating generated from exon 4 crh ‐ 1 gene (circ‐ ). Here, we that biogenesis circ‐ was regulated...

10.1111/acel.13560 article EN Aging Cell 2022-01-31

To identify novel components in heterotrimeric G-protein signalling, we performed an extensive screen for proteins interacting with Caenorhabditis elegans Galpha subunits. The genome of C. contains homologues each the four mammalian classes subunits (Gs, Gi/o, Gq and G12), 17 other We tested 19 GGalpha constitutively activated a largescale yeast two-hybrid experiment. This resulted identification 24 clones, representing 11 different that interact set includes orthologues known interactors...

10.1002/cfg.318 article EN cc-by Comparative and Functional Genomics 2003-10-01

We report here on a chemical genetic screen designed to address the mechanism of action small molecule. Small molecules that were active in models urinary incontinence tested nematode Caenorhabditis elegans, and resulting phenotypes used as readouts identify possible molecular targets. The mutations giving resistance compound found affect members RGS protein/G-protein complex. Studies mammalian systems confirmed inhibit muscarinic G-protein coupled receptor (GPCR) signaling involving G-αq...

10.1371/journal.pgen.0020057 article EN cc-by PLoS Genetics 2006-04-18

Abstract The generation of cellular diversity is dependent on the precise spatiotemporal regulation gene expression by both cis ‐ and trans ‐acting mechanisms. developmental principles regulating specific subsets in individual cell types are not fully understood. Here we define ‐regulatory mechanisms driving cell‐selective broadly expressed genes vivo AWB olfactory neuron subtype C. elegans . We identify an element that necessary to drive neuron‐selective chemoreceptor neurons, show this...

10.1002/dvdy.22147 article EN Developmental Dynamics 2009-11-18

ABSTRACT Circular RNAs (circRNAs) are non-coding mostly derived from exons of protein-coding genes via a back-splicing process. The expression hundreds circRNAs accumulates during healthy aging and is associated with Alzheimer’s disease (AD), characterized by the accumulation amyloid-beta (Aβ) proteins. In C. elegans , many were previously found to accumulate aging, loss age-accumulated CREB gene (circ- crh-1 ) increase mean lifespan. Here, we used study effects on age-related onset...

10.1101/2024.04.09.588761 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2024-04-13

Infection causes reduced activity, anorexia, and sleep, which are components of the phylogenetically conserved but poorly understood sickness behavior. We developed a Caenorhabditis elegans model to study quiescence during chronic infection, using infection with Orsay virus. The virus infects intestinal cells yet strongly affects behavior, indicating gut-to-nervous system communication. has sleep properties responsiveness rapid reversibility. Both ALA RIS neurons regulate virus-induced...

10.1523/jneurosci.1700-22.2024 article EN Journal of Neuroscience 2024-07-26

ABSTRACT Many lines of evidence point to links between sleep regulation and energy homeostasis, but mechanisms underlying these connections are unknown. During C. elegans sleep, energetic stores allocated non-neural tasks with a resultant drop in the overall fat charge. Mutants lacking KIN-29, homolog mammalian Salt-Inducible Kinase (SIK) that signals pressure, have low ATP levels despite high stores, indicating defective response cellular deficits. Liberating corrects adiposity defects...

10.1101/586701 preprint EN cc-by bioRxiv (Cold Spring Harbor Laboratory) 2019-03-22

We present a strategy to identify and map large numbers of transposon insertions in the genome Caenorhabditis elegans. Our approach makes use mutator strain mut-7, which has germline-transposition activity Tc1/mariner family transposons, display protocol detect new insertions, availability genomic sequence C. From pilot insertional mutagenesis screen, we have obtained 351 Tc1 transposons inserted or near 219 predicted elegans genes. The presented provides an isolate natural transposable...

10.1002/cfg.392 article EN cc-by Comparative and Functional Genomics 2004-04-01

Dynamic changes in chemoreceptor gene expression levels sensory neurons are one strategy that an animal can use to modify their responses dietary changes. However, the mechanisms underlying diet-dependent modulation of chemosensory unclear. Here, we show srh-234 localized a single ADL neuron type Caenorhabditis elegans is downregulated when animals fed Comamonas aquatica bacterial diet, but not on Escherichia coli diet. Remarkably, this diet-modulated effect dependent micronutrient vitamin...

10.1093/g3journal/jkac107 article EN cc-by G3 Genes Genomes Genetics 2022-05-04

Animals dramatically modify their chemosensory behaviors when starved, which could allow them to alter and optimize food-search strategies. Dynamic changes in the gene expression of chemoreceptors may be a general mechanism underlying food state-dependent behaviors. In our recent study,Citation1 we identified ADL sensory neuron type C. elegans that are modulated by feeding state availability. Here, highllight findings inputs into ADL, neuronal outputs from circuit RMG interneuron, is...

10.1080/21624054.2015.1023497 article EN Worm 2015-03-06
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