A5024059067- Genetics, Aging, and Longevity in Model Organisms
- Endoplasmic Reticulum Stress and Disease
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- Chromosomal and Genetic Variations
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Genomics, phytochemicals, and oxidative stress
- Coenzyme Q10 studies and effects
- Genetics and Neurodevelopmental Disorders
- Autophagy in Disease and Therapy
- Evolution and Genetic Dynamics
- Circadian rhythm and melatonin
- Pancreatic function and diabetes
- Pluripotent Stem Cells Research
- Virus-based gene therapy research
- Adipose Tissue and Metabolism
- Viral Infectious Diseases and Gene Expression in Insects
- Aquaculture Nutrition and Growth
- Amyotrophic Lateral Sclerosis Research
- Animal Genetics and Reproduction
- Lipid metabolism and biosynthesis
- Glutathione Transferases and Polymorphisms
- Advanced biosensing and bioanalysis techniques
- Biochemical Acid Research Studies
Fred Hutch Cancer Center
2021-2025
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2025
Harvard University
2016-2023
Massachusetts General Hospital
2016-2023
The Gurdon Institute
2008-2015
University of Cambridge
2008-2015
Wellcome Trust
2008-2015
Secondary Endogenous Small and Interfering In many eukaryotes, Piwi proteins bind small noncoding Piwi-interacting RNAs (piRNAs) that function to silence transposons in the germ line protect from transposable element–driven recombination mutation. Bagijn et al. (p. 574 , published online 14 June; see Perspective by Xiol Pillai ) show nematode, Caenorhabditis elegans a messenger RNA (mRNA) contains piRNA target sequence gives rise second, downstream class of known as secondary endogenous...
Proteasomes are essential for protein homeostasis in eukaryotes. To preserve cellular function, transcription of proteasome subunit genes is induced response to dysfunction caused by pathogen attacks or inhibitor drugs. In Caenorhabditis elegans, this requires SKN-1, a factor related mammalian Nrf1/2. Here, we use comprehensive genetic analyses identify the pathway required C. elegans detect and activate SKN-1. Genes SKN-1 activation encode regulators ER traffic, peptide N-glycanase, DDI-1,...
RNA interference defends against viral infection in plant and animal cells. The nematode Caenorhabditis elegans its natural pathogen, the positive-strand virus Orsay, have recently emerged as a new model of host-virus interaction. Using genome-wide association study C. wild populations quantitative trait locus mapping, we identify 159 base-pair deletion conserved drh-1 gene (encoding RIG-I-like helicase) major determinant sensitivity. We show that DRH-1 is required for initiation an...
In the nematode Caenorhabditis elegans, different small RNA-dependent gene silencing mechanisms act in germline to initiate transgenerational silencing. Piwi-interacting RNAs (piRNAs) can transposon and by acting upstream of endogenous short interfering (siRNAs), which engage a nuclear RNA interference (RNAi) pathway trigger transcriptional Once has been established, it be stably maintained over multiple generations without requirement initial is also referred as RNAe or paramutation. This...
Although excessive lipid accumulation is a hallmark of obesity-related pathologies, some lipids are beneficial. Oleic acid (OA), the most abundant monounsaturated fatty (FA), promotes health and longevity. Here, we show that OA benefits Caenorhabditis elegans by activating endoplasmic reticulum (ER)-resident transcription factor SKN-1A (Nrf1/NFE2L1) in homeostasis response. SKN-1A/Nrf1 cleared from ER ER-associated degradation (ERAD) machinery stabilized when proteasome activity low...
Unfolded protein responses (UPRs) safeguard cellular function during proteotoxic stress and aging. In a previous paper (Lehrbach Ruvkun, 2016) we showed that the ER-associated SKN-1A/Nrf1 transcription factor activates proteasome subunit expression in response to dysfunction, but it was not established whether adjusts capacity other insults. Here, reveal misfolded endogenous proteins human amyloid beta peptide trigger activation of by SKN-1A/Nrf1. SKN-1A is protective against age-dependent...
The Caenorhabditis elegans genome encodes nineteen functional Argonaute proteins that use 22G-RNAs, 26G-RNAs, miRNAs or piRNAs to regulate target transcripts. Only one is essential under normal laboratory conditions: CSR-1. While CSR-1 has been studied widely, nearly all studies have overlooked the fact csr-1 locus two isoforms. These isoforms differ by an additional 163 amino acids present in N-terminus of CSR-1a. Using CRISPR-Cas9 editing introduce GFP::3xFLAG into long (CSR-1a) and short...
Abstract microRNAs (miRNAs) are ∼22-nucleotide small RNAs that act as endogenous regulators of gene expression by base-pairing with target mRNAs. Here we analyze the function six members Caenorhabditis elegans miR-51 family miRNAs (miR-51, miR-52, miR-53, miR-54, miR-55, miR-56). broadly expressed from mid-embryogenesis onward. The is redundantly required for embryonic development. mir-51 mutants display a highly penetrant pharynx unattached (Pun) phenotype, where pharyngeal muscle, food...
ABSTRACT The Nrf/NFE2L family of transcription factors regulates redox balance, xenobiotic detoxification, metabolism, proteostasis, and aging. Nrf1/NFE2L1 is primarily responsible for stress-responsive upregulation proteasome subunit genes essential adaptation to proteotoxic stress. Nrf2/NFE2L2 mainly involved in activating oxidative stress responses promoting detoxification. Nrf1 Nrf2 contain very similar DNA binding domains can drive transcriptional responses. In C. elegans , a single...
Regulation of gene expression by microRNAs (miRNAs) is essential for normal development, but the roles miRNAs in physiology adult animals are poorly understood. We have isolated a conditional allele DGCR8 / pash-1 , which allows reversible and rapid inactivation miRNA synthesis vivo Caenorhabditis elegans . This powerful new tool that dissection post-developmental functions. demonstrate continuous dispensable cellular viability critical animals. Loss reduces lifespan results aging. The...
Several recent studies have provided evidence that LIN28, a cytoplasmic RNA-binding protein, inhibits the biogenesis of members let-7 microRNA family at Dicer step in both mammals and Caenorhabditis elegans. However, precise mechanism inhibition is still poorly understood. Here we report on an vitro study, which combined RNase footprinting, gel shift binding assays, processing to investigate molecular basis function interaction between native let-7g precursor (pre-let-7g) LIN28. We mapped...
daf-2 is one of the most studied mutants in C. elegans: it contains a deletion gene orthologue insulin/insulin-like growth factor (IGF) receptor. Using high resolution 1H NMR spectroscopy, metabolomics has helped to dissect metabolic consequences altered signalling. Here, we present detailed metabolomic analysis daf-2, using gas chromatography mass spectrometry (GC-MS) and liquid (LC-MS) integrate information from different pathways. We have then used Pearson partial correlation build...
Messenger RNA translation is regulated by RNA-binding proteins and small non-coding RNAs called microRNAs. Even though we know the majority of microRNAs that regulate messenger expression, evidence interactions between two remain elusive. The role protein GLD-1 as a translational repressor well studied during Caenorhabditis elegans germline development maintenance. Possible functions somatic mechanism how acts are not known. Its human homologue, quaking (QKI), essential for embryonic...
Abstract Forward genetic analysis using chemical mutagenesis in model organisms is a powerful tool for investigation of molecular mechanisms biological systems. In the nematode, Caenorhabditis elegans , screens ethyl methanesulfonate (EMS) have led to important insights into control animal development and physiology. A major bottleneck this approach identification causative mutation underlying phenotype interest. past, has required time‐consuming mapping experiments. More recently,...
Animals have evolved critical mechanisms to maintain cellular and organismal proteostasis during development, disease, exposure environmental stressors. The Unfolded Protein Response (UPR) is a conserved pathway that senses responds the accumulation of misfolded proteins in endoplasmic reticulum (ER) lumen. We previously demonstrated IRE-1-XBP-1 branch UPR required Caenorhabditis elegans ER homeostasis larval development presence pathogenic Pseudomonas aeruginosa In this study, we identify...
Transgenic animals are an invaluable tool in model organism genetics. The ease of modifying the
ABSTRACT Proteasomes are essential for protein homeostasis in eukaryotes. To preserve cellular function, transcription of proteasome subunit genes is induced response to dysfunction caused by pathogen attacks or inhibitor drugs. In Caenorhabditis elegans , this requires SKN-1, a factor related mammalian Nrf1/2. Here, we use comprehensive genetic analyses identify the pathway required C. detect and activate SKN-1. Genes SKN-1 activation encode regulators ER traffic, peptide N-glycanase,...