Biomedical subjects

Hannah R Nicholas

Publications and source records attributed to Hannah R Nicholas.

5 recordsLinked to original sources

PubMed2006

Solution structure of the THAP domain from Caenorhabditis elegans C-terminal binding protein (CtBP).

The THAP (Thanatos-associated protein) domain is a recently discovered zinc-binding domain found in proteins involved in transcriptional regulation, cell-cycle control, apoptosis and chromatin modification. It contains a single zinc atom ligated by cysteine and histidine residues within a Cys-X(2-4)-Cys-X(35-53)-Cys-X(2)-His consensus. We have determined the NMR solution structure of the THAP domain from Caenorhabditis elegans C-terminal binding protein (CtBP) and show that it adopts a fold containing a treble clef motif, bearing similarity to the zinc finger-associated domain (ZAD) from Drosophila Grauzone. The CtBP THAP domain contains a large, positively charged surface patch and we demonstrate that this domain can bind to double-stranded DNA in an electrophoretic mobility-shift assay. These data, together with existing reports, indicate that THAP domains might exhibit a functional diversity similar to that observed for classical and GATA-type zinc fingers.

Alcohol Oxidoreductases↗

PubMed2005

Multiple genes affect sensitivity of Caenorhabditis elegans to the bacterial pathogen Microbacterium nematophilum.

Interactions with bacteria play a major role in immune responses, ecology, and evolution of all animals, but they have been neglected until recently in the case of C. elegans. We report a genetic investigation of the interaction of C. elegans with the nematode-specific pathogen Microbacterium nematophilum, which colonizes the rectum and causes distinctive tail swelling in its host. A total of 121 mutants with altered response to infection were isolated from selections or screens for a bacterially unswollen (Bus) phenotype, using both chemical and transposon mutagenesis. Some of these correspond to known genes, affecting either bacterial adhesion or colonization (srf-2, srf-3, srf-5) or host swelling response (sur-2, egl-5). Most mutants define 15 new genes (bus-1-bus-6, bus-8, bus-10, bus-12-bus-18). The majority of these mutants exhibit little or no rectal infection when challenged with the pathogen and are probably altered in surface properties such that the bacteria can no longer infect worms. A number have corresponding alterations in lectin staining and cuticle fragility. Most of the uninfectable mutants grow better than wild type in the presence of the pathogen, but the sur-2 mutant is hypersensitive, indicating that the tail-swelling response is associated with a specific defense mechanism against this pathogen.

Actinomycetales↗

PubMed2004

The ERK MAP kinase cascade mediates tail swelling and a protective response to rectal infection in C. elegans.

The nematode Caenorhabditis elegans is proving to be an attractive model organism for investigating innate immune responses to infection. Among the known pathogens of C. elegans is the bacterium Microbacterium nematophilum, which adheres to the nematode rectum and postanal cuticle, inducing swelling of the underlying hypodermal tissue and causing mild constipation. We find that on infection by M. nematophilum, an extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase cascade mediates tail swelling and protects C. elegans from severe constipation, which would otherwise arrest development and cause sterility. Involvement in pathogen defense represents a new role for ERK MAP kinase signaling in this organism.

Actinomycetales↗

PubMed2004

Responses to infection and possible recognition strategies in the innate immune system of Caenorhabditis elegans.

In recent years, researchers investigating innate immunity have begun to use C. elegans as a new model system. The worm has been found to mount protective responses to a variety of fungal and bacterial pathogens. Four signalling pathways involved in such responses have been identified so far: the p38 MAP kinase pathway, the programmed cell death pathway, the TGF-beta pathway and the DAF-2 insulin/IGF-I like signalling pathway. Activation of these pathways can lead to the production of immune effector molecules such as lysozymes, lipases and saposin-like proteins, which can act directly against the invading microorganisms. The signalling pathways used and the effectors produced depend on the nature of the infection, indicating that the worm can detect and discriminate between infecting microorganisms. However, the molecules involved in recognition of pathogens have yet to be identified. The worm genome encodes various proteins which might have this recognition function, such as numerous proteins containing C-type lectin domains. These and other candidates are discussed.

Animals↗

PubMed2002

Innate immunity: the worm fights back.

Innate immunity is an evolutionarily ancient defense system that enables animals and plants to resist invading microorganisms. Recent studies have demonstrated the existence of innate immune responses in Caenorhabditis elegans.

Animals↗