Article
Immunology
Nestor L. Uzcategui, Sena Gucer, Cris Richter, Annika Speidel, Elizabeta Zirdum, Michael Duszenko, Olga Garaschuk, Katherine Figarella
Summary: Our study revealed the early involvement of microglia in Trypanosoma brucei infection before invasion of the CNS. We found that microglia have an exceptional capability to inhibit parasite proliferation inside the brain in areas of initial homeostatic disruption near brain barriers. Additionally, early signs of inflammation in the meninges synchronized with the microglial response, along with a massive infiltration of peripheral immune cells into the parenchyma during the final disease stage.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Anuj Tripathi, Ujjal K. Singha, Ayorinde Cooley, Taneisha Gillyard, Evan Krystofiak, Siddharth Pratap, Jamaine Davis, Minu Chaudhuri
Summary: TbTim50 is essential for mitochondrial function, regulation of kDNA replication, and the cell cycle in the bloodstream form of T. brucei. Depletion of TbTim50 results in inhibited cell growth, changes in morphology, increased AMPK phosphorylation, and upregulation of stumpy marker genes. TbTim50 is a crucial therapeutic target for African trypanosomiasis.
Article
Immunology
Yan-Zi Wen, Hao-Tian Tang, Xiao-Li Cai, Na Wu, Jia-Zhen Xu, Bi-Xiu Su, Geoff Hide, Zhao-Rong Lun, De-Hua Lai
Summary: In this study, PAG3 was identified as a key nuclear gene involved in the slender to stumpy differentiation pathway of Trypanosoma brucei in the mammalian host. The loss of this gene might explain the inability of T. evansi and some T. equiperdum to differentiate and the adaptation to transmission cycles that bypass the tsetse vector or mechanical contact.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Andrew Cowton, Peter Butikofer, Robert Haner, Anant K. Menon
Summary: In this study, two subunits TbGPI14 and TbPBN1 of Trypanosoma brucei GPI-mannosyltransferase-I (GPI-MT-I) were identified as crucial for GPI synthesis and surface expression of GPI-anchored proteins, forming a higher-order complex through interaction. The heterodimeric architecture and species specificity within GPI-MT-I subunit associations were demonstrated with the failure of yeast Gpi14 to restore function in TbGPI14 knockout trypanosomes. The essential role of a trypanosome GPI-MT-I subcomponent indicates wide conservation of the unusual complex structure in glycosyltransferases.
MOLECULAR MICROBIOLOGY
(2022)
Article
Microbiology
Larson Boundenga, Illich Manfred Mombo, Mouinga-Ondeme Augustin, Ngoubangoye Barthelemy, Patrice Makouloutou Nzassi, Nancy D. Moukodoum, Virginie Rougeron, Franck Prugnolle
Summary: Human African Trypanosomiasis is an infectious disease caused by protozoan parasites. Domestic animals may serve as reservoirs for trypanosomes, including the species responsible for the disease, T. brucei gambiense.
Review
Cell Biology
James Budzak, Gloria Rudenko
Summary: The African trypanosome Trypanosoma brucei has a dense layer of Variant Surface Glycoprotein (VSG) coat that protects it from immune attack. High levels of RNA transcription and pre-mRNA processing, as well as chromatin rearrangement, are important for the abundant expression of VSG.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Manish Gupta, Alexander J. Pak, Gregory A. Voth
Summary: Researchers use molecular dynamics simulations to reveal the molecular mechanism of HIV-1 capsid formation, including the role of IP6. This study shows that IP6 initially promotes curvature generation by trapping pentameric defects and shifts the assembly behavior towards kinetically favored outcomes. Additionally, IP6 can stabilize metastable capsid intermediates and induce structural pleomorphism in mature capsids.
Article
Biochemical Research Methods
Adam C. Swensen, Dusan Velickovic, Sarah M. Williams, Ronald J. Moore, Le Z. Day, Sherry Niessen, Sarah Hennessy, Camilo Posso, Mara Monetti, Wei-Jun Qian, Jon Jacobs, Laurence Whiteley, Ying Zhu, Paul D. Piehowski
Summary: Despite their small size, islets of Langerhans play a crucial role in maintaining systemic energy balance in the body. This study uses advanced technologies to investigate the protein profiles of different features within the islet, revealing unique protein signatures in the inner vasculature that indicate increased innervation and intra-islet neuron-like crosstalk. The data also prove useful in identifying localized structure-specific drug-target interactions.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Cell Biology
Jan Pyrih, Michael Hammond, Aline Alves, Samuel Dean, Jack Daniel Sunter, Richard John Wheeler, Keith Gull, Julius Lukes
Summary: The generated MitoTag dataset provides new insights into the mitochondrial proteome of Trypanosoma brucei, identifying previously undescribed proteins and revealing sub-compartment localization and novel metabolic pathways.
Article
Infectious Diseases
Nofar Baron, Nitin Tupperwar, Irit Dahan, Uzi Hadad, Geula Davidov, Raz Zarivach, Michal Shapira
Summary: Leishmania parasites cycle between sand-fly vectors and mammalian hosts, adapting to changing environments through stage-specific gene expression regulation. Translation initiation is controlled post-transcriptionally in Leishmania, with LeishIF4E2 showing unique characteristics and functions that differ from other translation factors. Deletion of one LeishIF4E2 gene copy led to altered morphology, changes in proteome profiles, and impaired infectivity in macrophages, suggesting specific functions for individual LeishIF4Es.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Biology
Wenxin Hu, Hongjin Zheng
Summary: Wenxin Hu et al. used cryo-EM and biochemical assays to describe the functional activity and structure of the ferrichrome importer, FhuCDB in E. coli. Their results reveal a new structural twist in the type II ABC importer subfamily and provide biological insights in the transport of iron-chelated siderophores.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
James Budzak, Ione Goodwin, Calvin Tiengwe, Gloria Rudenko
Summary: Visualization of genomic loci is crucial for understanding nuclear organization, and the LacO-LacI system provides a powerful approach for studying their positioning. We have optimized this system with short and stabilized LacO repeats, paired with a fluorescently tagged LacI protein, to visualize genomic loci. The compatibility with super-resolution microscopy and its potential for multiplexing with gene expression perturbation techniques make this system highly suitable for studying nuclear organization.
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2023)
Article
Physics, Fluids & Plasmas
Palash Bera, Abdul Wasim, Jagannath Mondal
Summary: In this study, the complex dynamics of Escherichia coli chromosome in the cytoplasm was investigated. By simulating the genome-wide spectrum of chromosomal loci and analyzing the Hi-C interaction matrix, it was found that the diffusion of the chromosome is subdiffusive and highly dependent on the coordinates of chromosomal loci. The dynamics are heterogeneous and modulated by genetically distant interactions, which play a key role in the underlying heterogeneity of loci diffusion.
Article
Biochemistry & Molecular Biology
Mark J. Girasol, Emma M. Briggs, Catarina A. Marques, Jose M. Batista, Dario Beraldi, Richard Burchmore, Leandro Lemgruber, Richard McCulloch
Summary: This study identifies and characterizes proteins that interact with RNA-DNA hybrids in the African trypanosome, revealing their diverse and important roles in host immune evasion and eukaryotic genome function.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Clement Pichot, Anis Djari, Joseph Tran, Marion Verdenaud, William Marande, Cecile Huneau, Veronique Gautier, David Latrasse, Sandrine Arribat, Vivien Sommard, Christelle Troadec, Charles Poncet, Mohammed Bendahmane, Judit Szecsi, Catherine Dogimont, Jerome Salse, Moussa Benhamed, Mohamed Zouine, Adnane Boualem, Abdelhafid Bendahmane
Summary: This study provides insights into the diversity and evolution of melon, and offers comprehensive genomic resources for further research.
Article
Biochemistry & Molecular Biology
Naomichi Takemata, Stephen D. Bell
Summary: Chromosome conformation capture technologies have identified topologically associating domains and A/B compartments as key features of eukaryotic chromosomes, with Sulfolobus archaea chromosomes also showing unique characteristics. The study reveals local rules governing the organization of topological domains and provides insights into the evolution of eukaryotic chromosome conformation through analysis of prokaryotic chromosome structures.
Article
Microbiology
Peter B. Bohall, Stephen D. Bell
Summary: The loss of putative repair polymerases PolB2 and/or PolB3 in the crenarchaeon Sulfolobus islandicus leads to a modest growth advantage and insensitivity to hydrogen peroxide. However, cells lacking PolB3 show enhanced sensitivity to the DNA damaging agent 4-NQO, suggesting that these non-essential DNA polymerases may influence DNA repair pathway choice in hyperthermophilic aerobes.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Microbiology
Carla Gilabert Carbajo, Lucy J. Cornell, Youssef Madbouly, Zhihao Lai, Phillip A. Yates, Michele Tinti, Calvin Tiengwe
Summary: Iron deprivation in Trypanosoma brucei induces upregulation of TfR, parasite-specific genes, glucose uptake and glycolysis genes, endocytosis genes, and a divergent RNA binding protein RBP5. Cells depleted of TfR import free iron as a survival strategy. RBP5 expression is regulated post-transcriptionally and above a certain threshold is toxic, affecting cell cycle progression. This study sheds new light on the mechanisms by which T. brucei handles iron stress.
Article
Biochemistry & Molecular Biology
Ivana Rubic, Richard Burchmore, Stefan Weidt, Clement Regnault, Josipa Kules, Renata Baric Rafaj, Tomislav Masek, Anita Horvatic, Martina Crnogaj, Peter David Eckersall, Predrag Novak, Vladimir Mrljak
Summary: This study aimed to explore and characterize the serum metabolome of dogs naturally infected with Babesia canis. By using different analytical platforms, 295 metabolites were detected and various metabolic pathways were found to be involved in canine babesiosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Mark D. Greci, Joseph D. Dooher, Stephen D. Bell
Summary: Recent research has discovered that archaeal primases have the unique ability to first synthesize RNA before randomly incorporating a deoxyribonucleotide, promoting hand-off of the primer to the replicative DNA polymerase and serving as an optimal substrate for primer elongation.
NATURE COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Jitkasem Meewan, Sukrut Somani, Partha Laskar, Craig Irving, Margaret Mullin, Stuart Woods, Craig W. Roberts, Abdullah R. Alzahrani, Valerie A. Ferro, Suzanne McGill, Stefan Weidt, Richard Burchmore, Christine Dufes
Summary: The protein corona formed on the nanoparticle surface has a strong influence on cell interactions and uptake of nanomedicines. This study shows that the protein corona affects the uptake of PEGylated zein micelles by cancer cells, macrophages, and dendritic cells. PEGylation gives stealth effects to the zein micelles and makes them promising drug delivery systems for cancer therapy.
Article
Biochemical Research Methods
Heather Hulme, Lynsey M. Meikle, Nicole Strittmatter, John Swales, Gregory Hamm, Sheila L. Brown, Simon Milling, Andrew S. MacDonald, Richard J. A. Goodwin, Richard Burchmore, Daniel M. Wall
Summary: Microbes have significant effects on the levels of neurotransmitters and their precursors in the brain. Antibiotic treatment does not cause significant changes in these metabolites in the brain.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Microbiology
Catherine Badel, Rachel Y. Samson, Stephen D. Bell
Summary: The DNA sequence and structural organization of chromosomes affect gene expression. Sulfolobus, a type of thermophilic crenarchaeon, has a circular chromosome with three replication origins and A, B compartments. The distance from a replication origin is associated with increased mutation rates in the B compartment, while sequences in the A compartment are less likely to be mutated and have stronger purifying selection. The B compartment is less accessible than the A compartment. These findings suggest that chromosomal compartmentalization can influence chromosome evolution in Sulfolobus.
NATURE MICROBIOLOGY
(2022)
Article
Biology
Pornchai Anuntasomboon, Suradej Siripattanapipong, Sasimanas Unajak, Kiattawee Choowongkomon, Richard Burchmore, Saovanee Leelayoova, Mathirut Mungthin, Teerasak E-kobon
Summary: This study successfully sequenced the draft genomes of two Leishmania species in southern Thailand and found species-level similarity and genetic variation compared to the northern isolates. The unique proteins identified in these strains could be targeted for further experimental characterization. These findings indicate the need for more genetic and population genomic investigation and close monitoring of these Leishmania species in Thailand and neighboring regions.
Article
Biochemistry & Molecular Biology
Mustafa M. Aldfer, Tahani A. AlSiari, Hamza A. A. Elati, Manal J. Natto, Ibrahim A. Alfayez, Gustavo D. Campagnaro, Bashiru Sani, Richard J. S. Burchmore, George Diallinas, Harry P. De Koning
Summary: The study of transporters, specifically nucleoside transporters, presents unique challenges and requires specific systems for analysis. This study describes the development of a system, using CRISPR/Cas9 technology, to delete and reintroduce nucleoside transporters in Leishmania mexicana, providing a null background for the expression and characterization of individual transporter genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Pornchai Anuntasomboon, Suradej Siripattanapipong, Sasimanas Unajak, Kiattawee Choowongkomon, Richard Burchmore, Saovanee Leelayoova, Mathirut Mungthin, Teerasak E-kobon
Summary: This study presents an integrative bioinformatic workflow for assembling the high-quality genome of Leishmania orientalis strain PCM2 from Thailand using short-read data. The workflow provides extensive information for identifying strain-specific markers and virulence-associated genes, which is useful for drug and vaccine development.
Review
Biochemistry & Molecular Biology
Stephen D. Bell
Summary: The key principle of modernist architecture is that 'form follows function', and chromosome architecture in archaea is shaped by evolutionary forces. Although the mechanistic details of archaeal chromosome organization are not yet fully understood, some general principles have emerged. Gene expression profiles influence chromosome architecture, and changes in chromosome conformation can also influence gene expression.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Marzuq A. Ungogo, Mustafa M. Aldfer, Manal J. Natto, Hainan Zhuang, Robyn Chisholm, Katy Walsh, MarieClaire McGee, Kayhan Ilbeigi, Jamal Ibrahim Asseri, Richard J. S. Burchmore, Guy Caljon, Serge Van Calenbergh, Harry P. De Koning
Summary: African Animal Trypanosomiasis (AAT) is a fatal livestock disease in Sub-Saharan Africa caused by Trypanosoma brucei brucei, T. vivax, and T. congolense. Limited treatment options and resistance threaten the control of this disease. In this study, the adenosine transporters of T. vivax (TvxNT3) and T. congolense (TcoAT1/NT10) were characterized and their functional expression was demonstrated. The findings suggest that nucleoside chemotherapy for AAT is viable based on the similarities in nucleoside sensitivity among different parasite species and the interactions with nucleoside transporters.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ivana Rubic, Stefan Weidt, Richard Burchmore, Alan Kovacevic, Josipa Kules, Peter David Eckersall, Marin Torti, Ines Jovic, Mislav Kovacic, Jelena Gotic, Renata Baric Rafaj, Predrag Novak, Marko Samardzija, Vladimir Mrljak
Summary: This study utilized mass spectrometry-based analysis to compare changes in plasma metabolites between dogs with idiopathic dilated cardiomyopathy (iDCM) and healthy dogs. The findings revealed altered concentrations of various metabolites involved in the development of iDCM. These results will contribute to the detection and monitoring of pathophysiological mechanisms in the development of iDCM in the future.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Martha Lucia Diaz, Karl Burgess, Richard Burchmore, Maria Adelaida Gomez, Sergio Alejandro Gomez-Ochoa, Luis Eduardo Echeverria, Carlos Morillo, Clara Isabel Gonzalez
Summary: This exploratory study used metabolomic profiling to investigate the underlying pathogenic mechanisms in the failing myocardium of patients with end-stage heart failure secondary to chronic Chagas cardiomyopathy (CCC). The results revealed altered metabolite profiles associated with energy deficit, changes in substrate availability, and increased production of reactive oxygen species in the affected myocardium.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
