Cryptosporidium and cryptosporidiosis
Cryptosporidiosis is a diarrheal disease caused by Cryptosporidium, a pathogen of significant medical concern that has gained public attention multiple times in recent decades. Despite its impact, there are currently no effective drugs or vaccines available to treat or prevent cryptosporidiosis. This disease primarily affects young children under the age of five and individuals with weakened immune systems, often resulting in severe, prolonged diarrhoea that can lead to life-threatening dehydration.
Research on the infection dynamics of Cryptosporidium and its interactions with host cells has been challenging due to the absence of reliable laboratory systems for observing its infection and replication. However, our laboratory has pioneered methods to overcome these challenges by infecting various cancer cell lines, creating a model that allows us to study the parasite’s growth and replication within host cells.
Our current research focuses on elucidating the specific metabolites Cryptosporidium extracts from the hosts and understanding how it manipulates host molecular mechanisms for its survival and proliferation. Additionally, we are investigating the cellular positioning of Cryptosporidium in both intra- and extracellular environments, along with the evolutionary adaptations that contribute to its success as a parasite.
Upper photo: Cryptosporidium oocysts stained with Crypto-glo and captured with fluorescence microscope (picture captured by Alexander Bones).
Bottom photo: Cryptosporidium oocysts captures with Scanning electron microscope (picture captured by Tansy Vallintine).
Establishing Naegleria as a model system to investigate adaptations to eukaryotic cellular adaptations
This project aims to develop tools and use them to study an organism that is neither animal, plant, algae, nor parasite. It is a single-celled creature living in soils and freshwater around the world. This creature, Naegleria gruberi, possesses nearly all of the cellular features found in animal and plant cells, but evolved away from them nearly 1.5 billion years ago. It is a uniquely placed sampling point from which to collect information about how cells work and gain a global perspective applicable to all eukaryotic cells. Our laboratory is currently developing a state-of-the-art genome editing system based on CRISPR/Cas9 based methodology. This will enable the systematic interrogation of Naegleria's genome function by making this organism amenable to the full array of CRISPR-based approaches currently established for other organisms, including knockout, knockdown and activation screens of various genes. We will aim to develop this approach into a powerful high-throughput functional genomics toolbox, thereby enabling understanding of the function(s) of the 15,727 protein-coding genes that are present in Naegleria’s nuclear genome. The overall outcome of this project is to produce a set of protocols, plasmids and tools to be used by the scientific community to address diverse scientific questions, using Naegleria gruberi as a model system.
Exploring the anaerobic and other unique adaptations of Blastocystis
Blastocystis is an obligate anaerobic parasite also found in patients with irritable bowel syndrome. The actual pathogenicity of Blastocystisis still questionable, since currently there is no direct link between the parasite and the disease caused. As an anaerobic organism, Blastocystis harbor peculiar Mitochondrion-related organelles (MROs), which are considered to be an intermediate form between a typical mitochondrion and a hydrogenosome. Another interesting fact about Blastocystis, concerns the presence of peculiar proteins encoded from its genome: it seems that Blastocystis is a "lateral gene transfer magnet" since several genes have been acquired from diverse eukaryotes and prokaryotes in order to assemble a kind of mixed genome. Using a combination of bioinformatics along with cellular and biochemical techniques, our laboratory aims to investigate these “novel” functions in Blastocystis and its closely relatives (e.g. Proteromonas) and attempt to understand their evolutionary history and the reason for their existence.
Host-parasite interactions in the gut and how parasites shape the host’s microbiome
The gut is a complex ecosystem where diverse microbial communities coexist, interact, and compete, playing essential roles in host health and disease. Among these gut inhabitants are parasites, which engage in intricate interactions with their hosts and the microbiome, influencing both microbial dynamics and host physiology. Understanding these interactions is crucial for comprehending how parasites contribute to health, disease, and the overall structure of the gut microbiome.
Parasites can significantly alter the composition and function of the microbiome. Some parasites release bioactive molecules that manipulate the host's immune response, creating an environment that supports their survival while potentially altering microbial diversity. Others directly compete with commensal microbes for resources, leading to shifts in microbial populations that can impact the host’s immune function, nutrient absorption, and gut homeostasis. These interactions often have cascading effects, influencing susceptibility to infections and metabolic disorders.
In our lab, we focus on the interplay between gut parasites, such as Blastocystis and Cryptosporidium, and the host’s microbiome. By investigating how these parasites manipulate microbial communities and host cellular mechanisms, we aim to reveal the broader impact of parasitic infections on gut health. Specifically, we study the metabolites parasites consume or modify within the host and how these interactions influence microbial composition. Our research also explores the evolutionary adaptations of these parasites that enable them to navigate and thrive within complex microbial ecosystems.
Our work is enriched by collaborations with researchers in low- and middle-income countries (LMICs), including Somalia, Bangladesh, Thailand, and Algeria, among others. We welcome additional collaborators interested in contributing to this research, as expanding our network enhances our ability to address parasitic diseases and the microbiome's role in health on a global scale.
Through a combination of multi-omics analyses and advanced imaging techniques, we aim to elucidate the mechanisms by which parasites shape the microbiome. This work is essential not only for understanding parasitic diseases but also for identifying potential microbiome-based therapies that could mitigate the impacts of parasitic infections on the host.
Figure demonstrating the Blastocystis subtypes found in animals from the Wildwood Park (Kent) in our recent publication from Betts et al., 2018. Figure prepared by Emma Betts.
Anastasios Tsaousis displaying palpable enthusiasm, while collecting bison’s faeces (picture kindly provided by Nicola Baker)