Lesley T. MacNeil

ORCID: 0000-0001-9562-8754
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About
Contact & Profiles
Research Areas
  • Genetics, Aging, and Longevity in Model Organisms
  • Circadian rhythm and melatonin
  • Gut microbiota and health
  • Bacterial biofilms and quorum sensing
  • Gene Regulatory Network Analysis
  • Renal and related cancers
  • Tryptophan and brain disorders
  • Diet and metabolism studies
  • CRISPR and Genetic Engineering
  • Biochemical and Structural Characterization
  • Digital Imaging for Blood Diseases
  • Nutrition, Genetics, and Disease
  • TGF-β signaling in diseases
  • Birth, Development, and Health
  • Antifungal resistance and susceptibility
  • Dietary Effects on Health
  • Plant Molecular Biology Research
  • Microbial Natural Products and Biosynthesis
  • Vibrio bacteria research studies
  • Genomics, phytochemicals, and oxidative stress
  • Genetics, Bioinformatics, and Biomedical Research
  • Antibiotic Resistance in Bacteria
  • Axon Guidance and Neuronal Signaling
  • Genetic and Kidney Cyst Diseases
  • Alkaloids: synthesis and pharmacology

McMaster University
2009-2025

Digestive Health Research Institute
2020-2024

Population Health Research Institute
2017-2023

Hamilton Health Sciences
2023

University of Massachusetts Chan Medical School
2010-2018

York University
2017

Massachusetts Academy of Math and Science
2013

Center for Systems Biology
2013

Institute of Molecular Medicine
2013

University of Toronto
2006-2010

In any given cell, thousands of genes are expressed and work in concert to ensure the cell's function, fitness, survival. Each gene, turn, must be at proper time amounts appropriate functional outcome. The regulation expression some highly robust; their is controlled by invariable programs. For instance, developmental gene extremely similar a cell type from one individual another. other more variable: Their levels noisy different individual. This can beneficial physiological responses...

10.1101/gr.097378.109 article EN cc-by-nc Genome Research 2011-02-04

Highlights•Interspecies systems biology paradigm links genetics to metabolites•Vitamin B12 is produced by the Comamonas, but not E. coli, diet•Vitamin affects development, fertility, and propionic acid toxicity•Vitamin accelerates development via SAM metabolismSummaryDiet greatly influences gene expression physiology. In mammals, elucidating effects mechanisms of individual nutrients challenging due complexity both animal its diet. Here, we used an interspecies approach with Caenorhabditis...

10.1016/j.cell.2014.01.047 article EN publisher-specific-oa Cell 2014-02-01

RNAi has become an essential tool in C. elegans research. Procedures for by microinjecting with dsRNA, feeding bacteria expressing dsRNA and soaking solution are described this unit.

10.1002/0471142727.mb2603s109 article EN Current Protocols in Molecular Biology 2015-01-01

Bacteria living in the human gut are implicated etiology of several diseases. Moreover, dozens drugs metabolized by elements microbiome, which may have further implications for health. Here, we screened a collection isolates their ability to inactivate widely used antineoplastic drug doxorubicin and identified strain Raoultella planticola as potent inactivator under anaerobic conditions. We demonstrate that R. deglycosylates metabolites 7-deoxydoxorubicinol 7-deoxydoxorubicinolone via...

10.1021/acsinfecdis.7b00166 article EN ACS Infectious Diseases 2017-11-21

Type IV pili are expressed by a wide range of prokaryotes, including the opportunistic pathogen Pseudomonas aeruginosa. These flexible fibres mediate twitching motility, biofilm maturation, surface adhesion, and virulence. The pilus is composed mainly major pilin subunits while low abundance minor pilins FimU-PilVWXE putative adhesin PilY1 prime assembly proposed to form tip. encoded in an operon that positively regulated FimS-AlgR two-component system. Independent assembly, was be...

10.1371/journal.ppat.1007074 article EN cc-by PLoS Pathogens 2018-05-18

Insulin/IGF-1 signaling plays a central role in longevity across phylogeny. In C. elegans, the forkhead box O (FOXO) transcription factor, DAF-16, is primary target of insulin/IGF-1 signaling, and multiple isoforms DAF-16 (a, b, d/f) modulate lifespan, metabolism, dauer formation, stress resistance. Thus far, phylogeny modulation mammalian FOXOs have focused on post-translational regulation with little focus transcriptional regulation. we previously shown that DAF-16d/f cooperates DAF-16a to...

10.1186/2046-2395-3-5 article EN cc-by Longevity & Healthspan 2014-04-23

Fungal infections cause millions of deaths annually and are challenging to treat due limited antifungal options increasing drug resistance. Cryptococci intrinsically resistant the latest generation antifungals, echinocandins, while Candida auris , a notorious global threat, is also increasingly resistant. We performed natural product extract screen for rescue activity echinocandin caspofungin against Cryptococcus neoformans H99, identifying butyrolactol A, which restores efficacy fungal...

10.1101/2025.01.06.630955 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2025-01-06

The rise of drug-resistant fungal pathogens, including Candida auris , highlights the urgent need for novel antifungal therapies. We developed a cost-effective platform combining microbial extract prefractionation with rapid MS/MS-bioinformatics-based dereplication to efficiently prioritize new scaffolds. Screening C. and albicans revealed lipopeptaibiotics, coniotins, from Coniochaeta hoffmannii WAC11161, which were undetectable in crude extracts. Coniotins exhibited potent activity against...

10.21203/rs.3.rs-5802877/v1 preprint EN cc-by Research Square (Research Square) 2025-01-17

ABSTRACT Type IVa pili (T4aP) are important virulence factors for many bacterial pathogens. Previous studies suggested that the retraction ATPase, PilT, modulates pathogenicity due to its critical role in pilus dynamics and twitching motility. Here we use a Caenorhabditis elegans slow-killing model show hyperpiliation, not loss of retraction, reduces Pseudomonas aeruginosa strains PAK PA14. Hyperactivating point mutations P. PilSR two-component system controls transcription major pilin gene,...

10.1128/spectrum.02558-24 article EN cc-by Microbiology Spectrum 2025-02-25

Parasitic worms are significant causes of human and livestock disease. The battle against infections caused by parasitic involves the exploration numerous potential drug candidates. One approach in screening for new candidates is using natural product extracts on nematode C. elegans as a model organism. A critical step this process examination microscopy images after exposure to extracts. Automatic image classification accelerates analysis compared purely visual identification an expert. We...

10.1109/jbhi.2025.3546603 article EN IEEE Journal of Biomedical and Health Informatics 2025-01-01

Cellular damage caused by reactive oxygen species is believed to be a major contributor age-associated diseases. Previously, we characterized the Caenorhabditis elegans Brap2 ortholog (BRAP-2) and found that it required prevent larval arrest in response elevated levels of oxidative stress. Here, report C. brap-2 mutants display increased expression SKN-1-dependent, phase II detoxification enzymes dependent on PMK-1 (a p38 MAPK ortholog). An RNA-interference screen was conducted using...

10.1534/genetics.116.198788 article EN Genetics 2017-06-10

Abstract The overproduction of reactive oxygen species (ROS) in cells can lead to the development diseases associated with aging. We have previously shown that C. elegansBRAP-2 (Brca1 binding protein 2) regulates phase II detoxification genes such as gst-4, by increasing SKN-1 activity. Previously, a transcription factor (TF) RNAi screen was conducted identify potential activators are required induce gst-4 expression brap-2(ok1492) mutants. lipid metabolism regulator NHR-49/HNF4 among 18 TFs...

10.1534/g3.118.200727 article EN cc-by G3 Genes Genomes Genetics 2018-10-09

Bone morphogenetic protein (BMP) pathways control an array of developmental and homeostatic events, must themselves be exquisitely controlled. Here, we identify Caenorhabditis elegans SMA-10 as a positive extracellular regulator BMP–like receptor signaling. acts genetically in (Sma/Mab) pathway between the ligand DBL-1 its receptors SMA-6 DAF-4. We cloned sma-10 show that it has fifteen leucine-rich repeats three immunoglobulin-like domains, hallmarks LRIG subfamily transmembrane proteins....

10.1371/journal.pgen.1000963 article EN cc-by PLoS Genetics 2010-05-20

C. elegans, both in the wild and lab, live on a diet of bacteria. The bacterial provides nutrients for but can also play number other roles elegans physiology. Recently, we compared effects different diets life history traits gene expression. Here, discuss our recent findings context dietary studies highlight challenges understanding effects. For instance, since bacteria be pathogenic it difficult to disentangle from Here summarize used how they affect animal.

10.4161/worm.26454 article EN Worm 2013-10-01
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