Download or read book Functional Characterization of Splicing associated Kinases in the Blood Stages of the Malaria Parasite Plasmodium Falciparum written by Selina Melanie Kern and published by . This book was released on 2015 with total page 296 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Functional Characterization of Four CDK like Kinases and One Calmodulin dependent Kinase of the Human Malaria Parasite Plasmodium Falciparum written by Shruti Agarwal and published by . This book was released on 2010 with total page 364 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Functional Analysis of Kinases in the Malaria Parasite Plasmodium Falciparum written by Eva Hitz and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Functional Characterization of Two Putative Telomere associated Proteins in the Malaria Parasite Plasmodium Falciparum written by Ajuh Elvis Tasih and published by . This book was released on 2013 with total page 176 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Functional Characterization of Selected Plasmodium Falciparum Protein Kinases written by Claudia Demarta and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Partial Characterization of Plasmodium Falciparum Protein Kinase ABCk2 PfABCk2 written by Muhammad Khalid and published by . This book was released on 2018 with total page 56 pages. Available in PDF, EPUB and Kindle. Book excerpt: There are approximately 100 protein kinases in P. falciparum that are involved in phosphorylation of asexual blood stage. Hence, the phosphorylation plays an important part in the development of different stages of malarial parasites. Due to their significance in the parasite life cycle, one of the protein kinase of P. falciparum belongs to the ABC-1 family of proteins. PfABCK2 can be a therapeutic target due to its higher expression during the late schizont stage of blood stage form.
Download or read book Heat Shock Proteins of Malaria written by Addmore Shonhai and published by Springer Nature. This book was released on 2021-09-26 with total page 256 pages. Available in PDF, EPUB and Kindle. Book excerpt: This new edition describes the role of heat shock proteins in the life cycle of malaria parasites, particularly in the context of intracellular parasite stages. Thoroughly revised, this work provides a general introduction to the structural and functional features of heat shock proteins with a special focus on their role as molecular chaperones in ensuring protein quality control. The emphasis is on the heat shock protein families from Plasmodium falciparum, and their role in proteostasis and the development of malaria pathology. Moreover, the authors explore the latest prospects of targeting heat shock proteins in antimalarial drug discovery either directly or in combination therapies. Readers will experience a functional analysis of the individual families of heat shock proteins and their cooperation in functional networks, including both the parasite-resident proteome and the exportome released into host cells during intracellular stages. Subcellular and extracellular organelles such as the apicoplast and the Maurer’s Clefts associated with Plasmodium species are discussed in detail. The book highlights the role of heat shock proteins in the development and function of these structures. Biochemical expertise and the inclusion of novel therapeutic solutions make this collection a unique reference for experts in heat shock protein research, parasitology and infectious diseases, cell stress, molecular biology and drug discovery. Not least, advances in malaria control will contribute to ending epidemics and ensuring healthy lives in line with the UN Sustainable Development Goals.
Download or read book Functional Characterization of Phospholipases During Blood Stage Development of Plasmodium Falciparum written by Emma Luise Pietsch and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterizing the Activity and Function of FIKK Kinases from the Malaria Parasite Plasmodium Falciparum written by Kathryn Scarbinsky and published by . This book was released on 2012 with total page 196 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Genome Engineering and Functional Gene Regulation Tools for the Study of Malaria Parasites written by Diana Alejandra Falla Castillo and published by . This book was released on 2018 with total page 201 pages. Available in PDF, EPUB and Kindle. Book excerpt: Plasmodium falciparum is the causative agent of the most severe form of human malaria, a mosquito-borne disease that remains a major global health problem. The efforts to create new antimalarial drugs and effective vaccines have been significantly hindered by the lack of robust tools for performing functional genetics in P. falciparum. The identification and characterization of essential functions for parasite survival are fundamental steps towards the creation of effective antimalarial therapies. In this work, we developed an integrated set of gene editing and functional gene regulation tools that enable the study of essential and non-essential genes in blood stage parasites. We first created a robust and versatile conditional expression system that uses a fusion of endogenous translational regulatory elements and synthetic RNA-protein modules to regulate gene expression in the parasite. Using this system, we achieved tight regulation of expression of reporter and essential antimalarial genes. Next, we created an integrated strategy that utilizes our conditional system together with a CRISPR-Cas9 gene editing system to identify and characterize the function of an essential RNA-Binding protein (RBP). We first determined the essentiality of our target protein using a two-step approach, in which a merodiploid line conditionally expresses an ectopic copy of the RBP and the native gene is disrupted using CRISPR technologies. This approach was next streamlined into a single-step methodology to genetically modify native loci to regulate expression from their promoters. We performed biochemical and biological characterization of this essential protein, and established the role of this RBP in cell cycle progression and parasite schizogony. Finally, to expand the repertoire of P.falciparum target loci, we implemented the editing activity of CRISPR-Cpfl, and showed high efficiency in the disruption of non-essential genes and genes located in AT-rich regions. We also integrated the Cpfl editing activity with our conditional system to achieve conditional regulation of native loci. This work combines genome-engineering technologies and regulatory systems designed to provide a robust platform for the identification and characterization of essential functions in human malarial parasites.
Download or read book Characterisation of the Eukaryotic Initiation Factor 2alpha Kinases of Plasmodium Falciparum written by Clare Fennell and published by . This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria remains a devastating disease with respect to both mortality and the constraints it places on the economic development of the countries in which it is endemic. Our laboratory is seeking new antimalarial targets, by characterising the protein kinases of the most lethal human malaria parasite, Plasmodium falciparum. As central components of many diverse signalling pathways, protein kinases are crucial for the control of proliferation and differentiation in other eukaryotes; we hypothesise that they play similar roles in P. falciparum. The life cycle of P. falciparum is complex, consisting of a series of tightly controlled stages of division and differentiation. In the related apicomplexan parasite Toxoplasma gondii, stress stimuli have been implicated in an important differentiation step, from rapidly dividing tachyzoites, to quiescent bradyzoites (which enable immune evasion). Evidence suggests that stress may also contribute to an essential differentiation stage, gametocytogenesis, in P. falciparum. In yeast and metazoans, part of the stress response is mediated through phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha), which results in selective translation of mRNAs encoding stress response proteins. Post-transcriptional control of gene expression is suspected to play an important role in P. falciparum. Importantly, the Goldberg laboratory recently demonstrated that similarly, in P. falciparum the eIF2alpha orthologue is phosphorylated in response to starvation. Here we identify the P. falciparum orthologue of the translation initiation factor eIF2alpha and provide bioinformatic evidence for the presence of three eIF2alpha kinases in P. falciparum; PfeIK1, PfeIK2 and PfPK4, only one of which (PfPK4) has been described previously (Mohrle et al., 1997). We show that one of the novel eIF2alpha kinases, PfeIK1, is able to phosphorylate P. falciparum eIF2alpha in vitro. In addition, initial experiments support previous observations that PfPK4 is indeed an active protein kinase (Mohrle et al., 1997). We present evidence that PfPK4 is essential for asexual growth, which precludes straightforward reverse genetics studies aiming to determine its possible role in gametocytogenesis. In contrast, transgenic parasites allowed us to show that neither PfeIK1 nor PfeIK2 are required for asexual growth, or sexual development of the parasite in the mosquito vector. However, preliminary evidence (requiring confirmation) may indicate that parasites lacking PfeIK1 over-express PfPK4, which would suggest that PfeIK1 may play an important function in the parasite. This study strongly suggests that a mechanism for versatile regulation of translation by several kinases with a similar catalytic domain, but distinct regulatory domains, is conserved in P. falciparum.
Download or read book Structural and Functional Characterization of Plasmodium Falciparum Nicotinic Acid Mononucleotide Adenylyltransferase written by and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Heterologous Expression and Functional Characterization of Plasmodium Falciparum ABCG in Mammalian Cells written by Khlood Ali AlSulami and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Malaria affects more than a quarter of this planet's population with 214 million infections and 438,000 deaths annually. In the absence of an effective malaria vaccine, the rise and spread of drug resistant strains coupled with the slow development of new antimalarials is a potential human tragedy. Research to date has led to the identification of several proteins that can mediate parasite resistance to most antimalarials. Two of the latter proteins (e.g., PfMDR1 and PfMRP1) are members of a large and evolutionary conserved family of ATP-dependent membrane transporters (e.g., ABC transporters). The P. falciparum genome encodes 16 different ABC transporters, including one member of the ABCG subfamily (e.g., PfABCG). By contrast, the human genome encodes 48 members of the ABC transporters, including five members of the ABCG subfamily (huABCG1, G2, G4, G5 and G8). With the exception of huABCG2, which transports many anti-cancer drugs and some normal cell metabolites, huABCG1, G4, G5 and G8 mediate the transport of cholesterol and other sterols. Earlier studies using PfABCG-knockout clones of P. falciparum have suggested that PfABCG may play a role in the parasite's sensitivity to ketotifen (an anti-histamine drug), and in the accumulation of neutral lipids in PfABCG-knockout clones. Moreover, we have shown that PfABCG shares 24.3 % and 26.5 % amino acid sequence identity with huABCG1 and huABCG2, respectively. Hence, it is presently not clear if PfABCG is functionally more like huABCG1, huABCG2, or both. In an effort to characterize the functions of PfABCG, it was of interest to compare its substrate specificity and subcellular localization to that of huABCG1 and G2 in the same expression system, using mammalian HEK-293 cells. Our results show the stable expression of PfABCG in HEK-293, as a fusion protein with GFP sequence linked to PfABCG N-terminal. In addition, relying on the fluorescence of GFP in PfABCG-HEK-293 transfectants, we have demonstrated the localization of GFP-PfABCG to the endosomal membranes, likely the endoplasmic reticulum. We also show that HEK-293 cells stably transfected with GFP-PfABCG are more sensitive to ketotifen in the presence of reseripine, a calcium channel blocker and an inhibitor of huABCB1 and huABCG2 expressed at low levels in HEK-293 cells. Efforts are on going to further characterize the functions of PfABCG and its substrate specificity and how these functions relate to those of huABCG1 and G2." --
Download or read book Identification and Functional Analysis of Proteins Involved in Host Cell Cytosol Uptake of the Human Malaria Parasite Plasmodium Falciparum written by Ricarda Sabitzki and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Functional Characterisation of the FIKK Kinase Family of Plasmodium Falciparum written by Hugo Marie Jean-Raymond Belda and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Identification of Plasmodium Falciparum Protein Kinase Substrates and Interacting Proteins written by Jessica C. Yap and published by . This book was released on 2012 with total page 45 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is a devastating disease that results in almost one million deaths annually. Most of the victims are children under the age of five in Sub-Saharan Africa. Malaria parasite strains throughout developing countries are continually building resistance to available drugs. Current therapies such as mefloquine, chloroquine, as well as artemisinin are becoming less effective, and this underscores the urgency for therapeutics directed against novel drug targets. In order to identify new drug targets, the molecular biology of the malaria parasite Plasmodium needs to be elucidated. Plasmodium exhibits a unique cell cycle in which it undergoes multiple rounds of DNA synthesis and mitosis without cytokinesis. Thus, cell cycle regulatory proteins are likely to be promising pathogen-specific drug targets. It is expected that fluctuating activity of key proteins, such as protein kinases, play an essential role in regulating the noncanonical life cycle of Plasmodium. Consequently, malarial kinases are a prime target for therapy. One way to better understand the role of malarial kinases in Plasmodium cell cycle regulation is to identify putative protein kinase substrates and interacting proteins. Two malarial kinases that have been implicated in regulating malaria parasite cell cycle stages were investigated in this study: P. falciparum CDK-like Protein Kinase 5 (PfPK5) and cAMP-Dependent Protein Kinase A (PfPKA). A transgenic P. falciparum line was created for the expression of epitope-tagged PfPK5 for pull-down analysis. Phospho-substrate antibodies were used to identify physiological substrates of both PfPK5 and PfPKA. Immunoblotting with these antibodies identified several potential substrates. Identities of the PfPKA physiological substrates were determined from the global P. falciparum phosphoproteome dataset that has recently been generated in our laboratory. Characterization of PfPKA and PfPK5 substrates, as well as the proteins they interact with, will help us to develop innovative therapies targeting binding sites.
