Project description:Toxoplasma gondii is an apicomplexan parasite infecting human and animals, causing huge health concerns and economic losses. Calcium ion, a critical second messenger in cells, can regulate related vital activities, particularly in parasite invasion and escape processes. Calmodulin (CaM) is a short, highly conserved Ca2+ binding protein found in all eukaryotic cells, including apicomplexan parasites. After binding to Ca2+, CaM can be activated to interact with a variety of proteins (such as enzymes). Since direct destruction of CaM is impossible, few studies have been conducted on the function of CaM in T. gondii. We generated the CaM indirect knockout strain (iCaM) using a tetracycline-off system with CaM promoter sequence in T. gondii TATI strain, and compared the transcriptomes of tachyzoites with and without Calmodulin.
2022-04-14 | GSE198001 | GEO
Project description:Multiple independent origins of apicomplexan-like parasites
| PRJNA539986 | ENA
Project description:Parallel evolution of reduced mitochondria in apicomplexan parasites
Project description:Genome organization in diverse eukaryotes follows conserved principles including the formation of chromosome territories (CT), chromatin compartments, and TADs. Here, we describe the 3D architecture of holocentric chromosomes in the silkworm Bombyx mori. At the genome-wide scale, B. mori chromosomes are highly territorial lacking any visible trans contact pattern. At the chromosomal scale, B. mori chromosomes segregate into three chromatin compartments: an active A and an inactive B as described in other eukaryotes, and a third type, X, with a unique contact pattern. Compartment X is strongly enriched for short-range interactions and depleted of long-range interactions, hosts a specific combination of genetic and epigenetic features and localizes towards the periphery of CT. Biophysical simulations reveal the necessity of the combined effects of affinity-based compartmentalization and activity-based loop extrusion to lead to the unique interaction patterns observed. Our analyses contribute to our understanding how chromosomes fold highlighting the evolutionary plasticity of 3D genome organization.
Project description:Our results demonstrate the utility of our Biop-C method in investigating the 3D genome organization in solid cancers, and the importance of 3D genome organization in regulating oncogenes in nasopharyngeal cancer.
Project description:Calcium Dependent Protein Kinases (CDPKs) are key effector in calcium signaling in Apicomplexan parasites. CDPK7 is one such kinase, which plays a crucial role in intracellular infection of Toxoplasma gondii parasite. To gain insights into how CDPK7 play a role in parasites survival, we have performed comparative phosphoproteomic to identify putative targets of TgCDPK7 in the parasites. Proteins from TgCDPK7 knockdown and wild were isolated, digested with trypsin and labelled with TMT. From the quantitative proteomic analysis by high- resolution mass spectrometry, differentially phosphorylated proteins were identified, which can be direct or indirect substrates of TgCDPK7. Many proteins which are involved in lipid metabolism are also found significantly altered.
Project description:To broadly explore artemisinin susceptibility in apicomplexan parasites, we used genome-scale CRISPR screens recently developed for Toxoplasma gondii to discover sensitizing and desensitizing mutations. From these screens, we identified the mitochondrial protease DegP2, which appeared gDegP2-responsive thermal stability in a pathway leading to decreased DHA susceptibility. To identify proteins exhibiting DegP2-responsive thermal stability
Project description:Toxoplasma gondii is an apicomplexan parasite infecting human and animals, causing huge health concerns and economic losses. Calcium ion, a critical second messenger in cells, can regulate related vital activities, particularly in parasite invasion and escape processes. Calmodulin (CaM) is a short, highly conserved Ca2+ binding protein found in all eukaryotic cells, including apicomplexan parasites. After binding to Ca2+, CaM can be activated to interact with a variety of proteins (such as enzymes). Nevertheless, CaM-interacting proteins have not been identified in T. gondii. We report here the use of T. gondii strain RH△hxgprt expressing the proximity-labeling enzyme BirA* fused to CaM, in combination with LC-MS/MS to specifically identify CaM-interacting proteins. Our study revealed over three hundred of CaM’s proximal interacting proteins in T. gondii. These CaM partners were broadly dispersed throughout the parasite. The majority of their CRISPR fitness scores were below zero, indicating CaM's essential functions in parasites.
Project description:The uploaded model is linked to the Scientific Reports article: Subramanian, A., Sarkar, R.R. Revealing the mystery of metabolic adaptations using a genome scale model of Leishmania infantum . Sci Rep 7, 10262 (2017). https://doi.org/10.1038/s41598-017-10743-x. Human macrophage phagolysosome and sandfly midgut provide antagonistic ecological niches for Leishmania parasites to survive and proliferate. Parasites optimize their metabolism to utilize the available inadequate resources by adapting to those environments. No genome-scale metabolic reconstruction was available for Leishmania infantum previously. Hence, we proposed a reconstructed genome-scale metabolic model for Leishmania infantum JPCM5, the analyses of which not only captures observations reported by metabolomics studies in other Leishmania species but also divulges novel features of the L. infantum metabolome. This manually reconstructed genome-scale metabolic network model (iAS556) contains 1260 reactions and 1160 metabolites. Our results indicate that Leishmania metabolism is organized in such a way that the parasite can select appropriate alternatives to compensate for limited external substrates. A dynamic non-essential amino acid motif exists within the network that promotes a restricted redistribution of resources to yield required essential metabolites. Further, subcellular compartments regulate this metabolic re-routing by reinforcing the physiological coupling of specific reactions. This unique metabolic organization is robust against accidental errors and provides a wide array of choices for the parasite to achieve optimal survival.