Veterinary Biosciences - Research Publications

Permanent URI for this collection

Search Results

Now showing 1 - 10 of 93
  • Item
    Thumbnail Image
    Artificial intelligence takes center stage: exploring the capabilities and implications of ChatGPT and other AI-assisted technologies in scientific research and education
    Borger, JG ; Ng, AP ; Anderton, H ; Ashdown, GW ; Auld, M ; Blewitt, ME ; Brown, D ; Call, MJ ; Collins, P ; Freytag, S ; Harrison, LC ; Hesping, E ; Hoysted, J ; Johnston, A ; Mcinneny, A ; Tang, P ; Whitehead, L ; Jex, A ; Naik, SH (WILEY, 2023-11)
    The emergence of large language models (LLMs) and assisted artificial intelligence (AI) technologies have revolutionized the way in which we interact with technology. A recent symposium at the Walter and Eliza Hall Institute explored the current practical applications of LLMs in medical research and canvassed the emerging ethical, legal and social implications for the use of AI-assisted technologies in the sciences. This paper provides an overview of the symposium's key themes and discussions delivered by diverse speakers, including early career researchers, group leaders, educators and policy-makers highlighting the opportunities and challenges that lie ahead for scientific researchers and educators as we continue to explore the potential of this cutting-edge and emerging technology.
  • Item
    No Preview Available
    Iron Supplementation May Selectively Reprofile the Gut Microbiome in Iron-Deficient Bangladeshi Infants
    Baldi, AJ ; Pasricha, S-R ; Jex, AR ; Hasan, MI ; Jones, N ; Barrios, M ; Braat, S ; Hamadani, J ; Wilcox, S ; Biggs, B-A ; Bowden, R (AMER SOC HEMATOLOGY, 2022-11-15)
  • Item
    No Preview Available
    Conservation, abundance, glycosylation profile, and localization of the TSP protein family in Cryptosporidium parvum
    John, A ; Bader, SM ; Soler, NM ; Wiradiputri, K ; Tichkule, S ; Smyth, ST ; Ralph, SA ; Jex, AR ; Scott, NE ; Tonkin, CJ ; Goddard-Borger, ED (ELSEVIER, 2023-03)
    Cryptosporidium parvum is a zoonotic apicomplexan parasite and a common cause of diarrheal disease worldwide. The development of vaccines to prevent or limit infection remains an important goal for tackling cryptosporidiosis. At present, the only approved vaccine against any apicomplexan parasite targets a conserved adhesin possessing a thrombospondin repeat domain. C. parvum possesses 12 orthologous thrombospondin repeat domain-containing proteins known as CpTSP1-12, though little is known about these potentially important antigens. Here, we explore the architecture and conservation of the CpTSP protein family, as well as their abundance at the protein level within the sporozoite stage of the life cycle. We examine the glycosylation states of these proteins using a combination of glycopeptide enrichment techniques to demonstrate that these proteins are modified with C-, O-, and N-linked glycans. Using expansion microscopy, and an antibody against the C-linked mannose that is unique to the CpTSP protein family within C. parvum, we show that these proteins are found both on the cell surface and in structures that resemble the secretory pathway of C. parvum sporozoites. Finally, we generated a polyclonal antibody against CpTSP1 to show that it is found at the cell surface and within micronemes, in a pattern reminiscent of other apicomplexan motility-associated adhesins, and is present both in sporozoites and meronts. This work sheds new light on an understudied family of C. parvum proteins that are likely to be important to both parasite biology and the development of vaccines against cryptosporidiosis.
  • Item
    Thumbnail Image
    VIVID A Web Application for Variant Interpretation and Visualization in Multi-dimensional Analyses
    Tichkule, S ; Myung, Y ; Naung, MT ; Ansell, BRE ; Guy, AJ ; Srivastava, N ; Mehra, S ; Caccio, SM ; Mueller, I ; Barry, AE ; van Oosterhout, C ; Pope, B ; Ascher, DB ; Jex, AR ; Teeling, E (OXFORD UNIV PRESS, 2022-09-01)
    Large-scale comparative genomics- and population genetic studies generate enormous amounts of polymorphism data in the form of DNA variants. Ultimately, the goal of many of these studies is to associate genetic variants to phenotypes or fitness. We introduce VIVID, an interactive, user-friendly web application that integrates a wide range of approaches for encoding genotypic to phenotypic information in any organism or disease, from an individual or population, in three-dimensional (3D) space. It allows mutation mapping and annotation, calculation of interactions and conservation scores, prediction of harmful effects, analysis of diversity and selection, and 3D visualization of genotypic information encoded in Variant Call Format on AlphaFold2 protein models. VIVID enables the rapid assessment of genes of interest in the study of adaptive evolution and the genetic load, and it helps prioritizing targets for experimental validation. We demonstrate the utility of VIVID by exploring the evolutionary genetics of the parasitic protist Plasmodium falciparum, revealing geographic variation in the signature of balancing selection in potential targets of functional antibodies.
  • Item
    Thumbnail Image
    Single-cell RNA profiling of Plasmodium vivax-infected hepatocytes reveals parasite- and host- specific transcriptomic signatures and therapeutic targets
    Ruberto, AA ; Maher, SP ; Vantaux, A ; Joyner, CJ ; Bourke, C ; Balan, B ; Jex, A ; Mueller, I ; Witkowski, B ; Kyle, DE (FRONTIERS MEDIA SA, 2022-08-25)
    The resilience of Plasmodium vivax, the most widely-distributed malaria-causing parasite in humans, is attributed to its ability to produce dormant liver forms known as hypnozoites, which can activate weeks, months, or even years after an initial mosquito bite. The factors underlying hypnozoite formation and activation are poorly understood, as is the parasite's influence on the host hepatocyte. Here, we shed light on transcriptome-wide signatures of both the parasite and the infected host cell by sequencing over 1,000 P. vivax-infected hepatocytes at single-cell resolution. We distinguish between replicating schizonts and hypnozoites at the transcriptional level, identifying key differences in transcripts encoding for RNA-binding proteins associated with cell fate. In infected hepatocytes, we show that genes associated with energy metabolism and antioxidant stress response are upregulated, and those involved in the host immune response downregulated, suggesting both schizonts and hypnozoites alter the host intracellular environment. The transcriptional markers in schizonts, hypnozoites, and infected hepatocytes revealed here pinpoint potential factors underlying dormancy and can inform therapeutic targets against P. vivax liver-stage infection.
  • Item
    Thumbnail Image
    Single-cell RNA sequencing of Plasmodium vivax sporozoites reveals stage- and species-specific transcriptomic signatures
    Ruberto, AA ; Bourke, C ; Vantaux, A ; Maher, SP ; Jex, A ; Witkowski, B ; Snounou, G ; Mueller, I ; Mireji, PO (PUBLIC LIBRARY SCIENCE, 2022-08)
    BACKGROUND: Plasmodium vivax sporozoites reside in the salivary glands of a mosquito before infecting a human host and causing malaria. Previous transcriptome-wide studies in populations of these parasite forms were limited in their ability to elucidate cell-to-cell variation, thereby masking cellular states potentially important in understanding malaria transmission outcomes. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we performed transcription profiling on 9,947 P. vivax sporozoites to assess the extent to which they differ at single-cell resolution. We show that sporozoites residing in the mosquito's salivary glands exist in distinct developmental states, as defined by their transcriptomic signatures. Additionally, relative to P. falciparum, P. vivax displays overlapping and unique gene usage patterns, highlighting conserved and species-specific gene programs. Notably, distinguishing P. vivax from P. falciparum were a subset of P. vivax sporozoites expressing genes associated with translational regulation and repression. Finally, our comparison of single-cell transcriptomic data from P. vivax sporozoite and erythrocytic forms reveals gene usage patterns unique to sporozoites. CONCLUSIONS/SIGNIFICANCE: In defining the transcriptomic signatures of individual P. vivax sporozoites, our work provides new insights into the factors driving their developmental trajectory and lays the groundwork for a more comprehensive P. vivax cell atlas.
  • Item
    Thumbnail Image
    3, 2, 1, go! Cryptosporidium counts down to sex
    Jex, AR ; Tonkin, CJ ; Ralph, SA (PUBLIC LIBRARY SCIENCE, 2022-05)
    Cryptosporidium is a leading cause of death from childhood diarrhea, but its biology is poorly understood. A recent study in PLOS Biology reveals hitherto unknown aspects of the parasite's life cycle that may lead to improvements in ex vivo culture.
  • Item
    Thumbnail Image
    Recent genetic exchanges and admixture shape the genome and population structure of the zoonotic pathogen Cryptosporidium parvum
    Corsi, G ; Tichkule, S ; Sannella, AR ; Vatta, P ; Asnicar, F ; Segata, N ; Jex, AR ; van Oosterhout, C ; Caccio, SM (WILEY, 2022-06-16)
    Cryptosporidium parvum is a globally distributed zoonotic pathogen and a major cause of diarrhoeal disease in humans and ruminants. The parasite's life cycle comprises an obligatory sexual phase, during which genetic exchanges can occur between previously isolated lineages. Here, we compare 32 whole genome sequences from human- and ruminant-derived parasite isolates collected across Europe, Egypt and China. We identify three strongly supported clusters that comprise a mix of isolates from different host species, geographic origins, and subtypes. We show that: (1) recombination occurs between ruminant isolates into human isolates; (2) these recombinant regions can be passed on to other human subtypes through gene flow and population admixture; (3) there have been multiple genetic exchanges, and most are probably recent; (4) putative virulence genes are significantly enriched within these genetic exchanges, and (5) this results in an increase in their nucleotide diversity. We carefully dissect the phylogenetic sequence of two genetic exchanges, illustrating the long-term evolutionary consequences of these events. Our results suggest that increased globalization and close human-animal contacts increase the opportunity for genetic exchanges between previously isolated parasite lineages, resulting in spillover and spillback events. We discuss how this can provide a novel substrate for natural selection at genes involved in host-parasite interactions, thereby potentially altering the dynamic coevolutionary equilibrium in the Red Queens arms race.
  • Item
    Thumbnail Image
    Global Population Genomics of Two Subspecies of Cryptosporidium hominis during 500 Years of Evolution
    Tichkule, S ; Caccio, SM ; Robinson, G ; Chalmers, RM ; Mueller, I ; Emery-Corbin, SJ ; Eibach, D ; Tyler, KM ; van Oosterhout, C ; Jex, AR ; Leitner, T (OXFORD UNIV PRESS, 2022-04-10)
    Cryptosporidiosis is a major global health problem and a primary cause of diarrhea, particularly in young children in low- and middle-income countries (LMICs). The zoonotic Cryptosporidium parvum and anthroponotic Cryptosporidium hominis cause most human infections. Here, we present a comprehensive whole-genome study of C. hominis, comprising 114 isolates from 16 countries within five continents. We detect two lineages with distinct biology and demography, which diverged circa 500 years ago. We consider these lineages two subspecies and propose the names C. hominis hominis and C. hominis aquapotentis (gp60 subtype IbA10G2). In our study, C. h. hominis is almost exclusively represented by isolates from LMICs in Africa and Asia and appears to have undergone recent population contraction. In contrast, C. h. aquapotentis was found in high-income countries, mainly in Europe, North America, and Oceania, and appears to be expanding. Notably, C. h. aquapotentis is associated with high rates of direct human-to-human transmission, which may explain its success in countries with well-developed environmental sanitation infrastructure. Intriguingly, we detected genomic regions of introgression following secondary contact between the subspecies. This resulted in high diversity and divergence in genomic islands of putative virulence genes, including muc5 (CHUDEA2_430) and a hypothetical protein (CHUDEA6_5270). This diversity is maintained by balancing selection, suggesting a co-evolutionary arms race with the host. Finally, we find that recent gene flow from C. h. aquapotentis to C. h. hominis, likely associated with increased human migration, maybe driving the evolution of more virulent C. hominis variants.
  • Item
    Thumbnail Image
    Precise gene models using long-read sequencing reveal a unique poly(A) signal in Giardia lamblia
    Bilodeau, DY ; Sheridan, RM ; Balan, B ; Jex, AR ; Rissland, OS (COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2022-05)
    During pre-mRNA processing, the poly(A) signal is recognized by a protein complex that ensures precise cleavage and polyadenylation of the nascent transcript. The location of this cleavage event establishes the length and sequence of the 3' UTR of an mRNA, thus determining much of its post-transcriptional fate. Using long-read sequencing, we characterize the polyadenylation signal and related sequences surrounding Giardia lamblia cleavage sites for over 2600 genes. We find that G. lamblia uses an AGURAA poly(A) signal, which differs from the mammalian AAUAAA. We also describe how G. lamblia lacks common auxiliary elements found in other eukaryotes, along with the proteins that recognize them. Further, we identify 133 genes with evidence of alternative polyadenylation. These results suggest that despite pared-down cleavage and polyadenylation machinery, 3' end formation still appears to be an important regulatory step for gene expression in G. lamblia.