Marilyn Parsons
Seattle Biomed
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Marilyn Parsons.
Molecular and Biochemical Parasitology | 1998
Christine Clayton; Mark D. Adams; Renata Almeida; Théo Baltz; Michael P. Barrett; Patrick Bastien; Sabina I. Belli; Stephen M. Beverley; Nicolas Biteau; Jenefer M. Blackwell; Christine Blaineau; Michael Boshart; Frédéric Bringaud; George A.M. Cross; Angela K. Cruz; Wim Degrave; John E. Donelson; Najib M. El-Sayed; Gioliang Fu; Klaus Ersfeld; Wendy Gibson; Keith Gull; Alasdair Ivens; John M. Kelly; Daniel Lawson; John Lebowitz; Phelix A.O. Majiwa; Keith R. Matthews; Sara E. Melville; Gilles Merlin
Christine Clayton *, Mark Adams , Renata Almeida , Theo Baltz , Mike Barrett , Patrick Bastien , Sabina Belli , Stephen Beverley , Nicolas Biteau , Jenefer Blackwell , Christine Blaineau , Michael Boshart , Frederic Bringaud , George Cross , Angela Cruz , Wim Degrave , John Donelson , Najib El-Sayed , Gioliang Fu , Klaus Ersfeld , Wendy Gibson , Keith Gull , Alasdair Ivens , John Kelly , Daniel Lawson , John Lebowitz , Phelix Majiwa , Keith Matthews , Sara Melville , Gilles Merlin , Paul Michels , Peter Myler , Alan Norrish , Fred Opperdoes , Barbara Papadopoulou , Marilyn Parsons , Thomas Seebeck , Deborah Smith , Kenneth Stuart , Michael Turner , Elisabetta Ullu , Luc Vanhamme aa
Molecular Microbiology | 2004
Marilyn Parsons
Peroxisomes are membrane‐bounded organelles that compartmentalize a variety of metabolic functions. Perhaps the most divergent peroxisomes known are the glycosomes of trypanosomes and their relatives. The glycolytic pathway of these organisms resides within the glycosome. The development of robust molecular genetic and proteomic approaches coupled with the completion of the genome sequence of the pathogens Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major provides an opportunity to determine the complement of proteins within the glycosome and the function of compartmentation. Studies now suggest that regulation of glycolysis is a strong driving force for maintenance of the glycosome.
Molecular and Cellular Biology | 1997
John A. Flaspohler; Wayne L. Rickoll; Stephen M. Beverley; Marilyn Parsons
Glycosomes are membrane-bounded microbody organelles that compartmentalize glycolysis as well as other important metabolic processes in trypanosomatids. The compartmentalization of these enzymatic reactions is hypothesized to play a crucial role in parasite physiology. Although the metabolic role of glycosomes differs substantially from that of the peroxisomes that are found in other eukaryotes, similarities in signals targeting proteins to these organelles suggest that glycosomes and peroxisomes may have evolved from a common ancestor. To examine this hypothesis, as well as gain insights into the function of the glycosome, we used a positive genetic selection procedure to isolate the first Leishmania mutant (gim1-1 [glycosome import] mutant) with a defect in the import of glycosomal proteins. The mutant retains glycosomes but mislocalizes a subset glycosomal proteins to the cytoplasm. Unexpectedly, the gim1-1 mutant lacks lipid bodies, suggesting a heretofore unknown role of the glycosome. We used genetic approaches to identify a gene, GIM1, that is able to restore import and lipid bodies. A nonsense mutation was found in one allele of this gene in the mutant line. The predicted Gim1 protein is related the peroxin 2 family of integral membrane proteins, which are required for peroxisome biogenesis. The similarities in sequence and function provide strong support for the common origin model of glycosomes and peroxisomes. The novel phenotype of gim1-1 and distinctive role of Leishmania glycosomes suggest that future studies of this system will provide a new perspective on microbody biogenesis and function.
Molecular and Biochemical Parasitology | 1993
Michael Gale; Marilyn Parsons
Using polymerase chain reaction technology we cloned a Trypanosoma brucei gene fragment that has a deduced amino acid sequence with a high degree of homology to protein kinase catalytic domains. This clone detects two genes by genomic Southern analysis. These genes, nrkA and nrkB, share a 97% nt sequence homology over their 1.3-kb coding regions. NrkA encodes a 48-kDa protein which possess all 11 protein kinase homology regions. The 279-aa N-terminal catalytic domain has highest homology with Nek1, a bifunctional kinase, and NIMA, a protein serine/threonine kinase. Both alleles at the nrkB locus in T. brucei strain IsTAR 1 encode a truncated protein kinase catalytic domain due the presence of a premature termination codon. However, the TREU667 strain is heterozygous at the nrkB locus, encoding one truncated and one full-length molecule. NrkA and NrkB possess multiple phosphorylation site motifs. Both nrk transcripts are constitutively expressed during parasite development.
Bioorganic & Medicinal Chemistry Letters | 2012
Zhongsheng Zhang; Kayode K. Ojo; Steven M. Johnson; Eric T. Larson; Penqing He; Jennifer A. Geiger; Alejandro Castellanos-Gonzalez; A. Clinton White; Marilyn Parsons; Ethan A. Merritt; Dustin J. Maly; Christophe L. M. J. Verlinde; Wesley C. Van Voorhis; Erkang Fan
Calcium-dependent protein kinase-1 (CDPK1) from Cryptosporidium parvum (CpCDPK1) and Toxoplasma gondii (TgCDPK1) have become attractive targets for discovering selective inhibitors to combat infections caused by these protozoa. We used structure-based design to improve a series of benzoylbenzimidazole-based compounds in terms of solubility, selectivity, and potency against CpCDPK1 and TgCDPK1. The best inhibitors show inhibitory potencies below 50 nM and selectivity well above 200-fold over two human kinases with small gatekeeper residues.
Molecular and Biochemical Parasitology | 1989
Marilyn Parsons; Teresa Hill
Phosphoglycerate kinase (PGK) is present in high levels in the glycosomes of bloodstream stage Trypanosoma brucei, but is virtually absent in procyclic stage glycosomes. Glycosomes isolated from slender and stumpy stage bloodforms show similar levels of PGK, although levels are slightly lower in stumpy forms. Lower levels of glycosomal PGK transcripts are observed in stumpy form RNA, paralleling the decrease in glycosomal PGK activity. Monomorphic strains and pleiomorphic strains show similar glycosomal PGK activity, but monomorphic strains have much higher levels of the glycosomal PGK transcript. In three separate cases, predominantly monomorphic strains derived from highly pleiomorphic strains showed increased levels of glycosomal PGK (gPGK) mRNA. gPGK synthesis rates in monomorphic and pleiomorphic strains were similar, and no significant differences in turnover were observed. These data suggest the possibility of translational control of gPGK protein levels in trypanosome bloodforms. The data also indicate that the metabolism of gPGK mRNA in highly passaged laboratory strains is altered, and counsel caution when attributing differences in transcript levels to stage-specific regulation.
Eukaryotic Cell | 2005
Bryan C. Jensen; Deirdre L. Brekken; Amber C. Randall; Charles T. Kifer; Marilyn Parsons
ABSTRACT In the protozoan parasite Trypanosoma brucei, the large rRNA, which is a single 3.4- to 5-kb species in most organisms, is further processed to form six distinct RNAs, two larger than 1 kb (LSU1 and LSU2) and four smaller than 220 bp. The small rRNA SR1 separates the two large RNAs, while the remaining small RNAs are clustered at the 3′ end of the precursor rRNA. One would predict that T. brucei possesses specific components to carry out these added processing events. We show here that the trypanosomatid-specific nucleolar phosphoprotein NOPP44/46 is involved in this further processing. Cells depleted of NOPP44/46 by RNA interference had a severe growth defect and demonstrated a defect in large-ribosomal-subunit biogenesis. Concurrent with this defect, a significant decrease in processing intermediates, particularly for SR1, was seen. In addition, we saw an accumulation of aberrant processing intermediates caused by cleavage within either LSU1 or LSU2. Though it is required for large-subunit biogenesis, we show that NOPP44/46 is not incorporated into the nascent particle. Thus, NOPP44/46 is an unusual protein in that it is both nonconserved and required for ribosome biogenesis.
Eukaryotic Cell | 2014
Savitha Kalidas; Igor Cestari; Severine Monnerat; Qiong Li; Sandesh Regmi; Nicholas Hasle; Mehdi Labaied; Marilyn Parsons; Kenneth Stuart; Margaret A. Phillips
ABSTRACT Human African trypanosomiasis (HAT) is an important public health threat in sub-Saharan Africa. Current drugs are unsatisfactory, and new drugs are being sought. Few validated enzyme targets are available to support drug discovery efforts, so our goal was to obtain essentiality data on genes with proven utility as drug targets. Aminoacyl-tRNA synthetases (aaRSs) are known drug targets for bacterial and fungal pathogens and are required for protein synthesis. Here we survey the essentiality of eight Trypanosoma brucei aaRSs by RNA interference (RNAi) gene expression knockdown, covering an enzyme from each major aaRS class: valyl-tRNA synthetase (ValRS) (class Ia), tryptophanyl-tRNA synthetase (TrpRS-1) (class Ib), arginyl-tRNA synthetase (ArgRS) (class Ic), glutamyl-tRNA synthetase (GluRS) (class 1c), threonyl-tRNA synthetase (ThrRS) (class IIa), asparaginyl-tRNA synthetase (AsnRS) (class IIb), and phenylalanyl-tRNA synthetase (α and β) (PheRS) (class IIc). Knockdown of mRNA encoding these enzymes in T. brucei mammalian stage parasites showed that all were essential for parasite growth and survival in vitro. The reduced expression resulted in growth, morphological, cell cycle, and DNA content abnormalities. ThrRS was characterized in greater detail, showing that the purified recombinant enzyme displayed ThrRS activity and that the protein localized to both the cytosol and mitochondrion. Borrelidin, a known inhibitor of ThrRS, was an inhibitor of T. brucei ThrRS and showed antitrypanosomal activity. The data show that aaRSs are essential for T. brucei survival and are likely to be excellent targets for drug discovery efforts.
Journal of Eukaryotic Microbiology | 2009
Marilyn Parsons; Anuradha Karnataki; Amy E. DeRocher
ABSTRACT. The apicoplast is a relict plastid found in many medically important apicomplexan parasites, such as Plasmodium and Toxoplasma. Phylogenetic analysis and the presence of four bounding membranes indicate that the apicoplast arose from a secondary endosymbiosis. Here we review what has been discovered about the complex journey proteins take to reach compartments of the apicoplast. The targeting sequences for luminal proteins are well‐defined, but those routing proteins to other compartments are only beginning to be studied. Recent work suggests that the trafficking mechanisms involve a variety of molecules of different phylogenetic origins. We highlight some remaining questions regarding protein trafficking to this divergent organelle.
Experimental Parasitology | 2017
Wesley C. Van Voorhis; J. Stone Doggett; Marilyn Parsons; Matthew A. Hulverson; Ryan Choi; Samuel L.M. Arnold; Michael W. Riggs; Andrew Hemphill; Daniel K. Howe; Robert H. Mealey; Audrey O.T. Lau; Ethan A. Merritt; Dustin J. Maly; Erkang Fan; Kayode K. Ojo
Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of parasitic diseases. However, the difficulty of inhibiting parasite protein kinases to the exclusion of host orthologues poses a practical challenge. A possible path around this difficulty is the use of bumped kinase inhibitors for targeting calcium-dependent protein kinases that contain atypically small gatekeeper residues and are crucial for pathogenic apicomplexan parasites survival and proliferation. In this article, we review efficacy against the kinase target, parasite growth inxa0vitro, and in animal infection models, as well as the relevant pharmacokinetic and safety parameters of bumped kinase inhibitors.