Download or read book A Novel Genetic System for the Functional Analysis of Essential Proteins of the Human Malaria Parasite Plasmodium Falciparum written by Jakob Birnbaum and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Malaria written by Institute of Medicine and published by National Academies Press. This book was released on 1991-02-01 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is making a dramatic comeback in the world. The disease is the foremost health challenge in Africa south of the Sahara, and people traveling to malarious areas are at increased risk of malaria-related sickness and death. This book examines the prospects for bringing malaria under control, with specific recommendations for U.S. policy, directions for research and program funding, and appropriate roles for federal and international agencies and the medical and public health communities. The volume reports on the current status of malaria research, prevention, and control efforts worldwide. The authors present study results and commentary on the: Nature, clinical manifestations, diagnosis, and epidemiology of malaria. Biology of the malaria parasite and its vector. Prospects for developing malaria vaccines and improved treatments. Economic, social, and behavioral factors in malaria control.

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 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 Analysis of Trophozoite and Schizont exported Proteins of the Human Malaria Parasite Plasmodium Falciparum Welch 1897 written by Jan Stäcker 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 A Novel RCC1 like Protein is a Crucial Regulator of the Intraerythrocytic Cycle of the Human Malaria Parasite Plasmodium Falciparum written by and published by . This book was released on 2015 with total page 58 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is a deadly infection caused by a single celled protozoan of the Plasmodium genus. Plasmodium spp. are transmitted to humans by mosquitoes, and initially invade the liver, but the disease is caused by the blood stage of the infection. Approximately 500 million cases of malaria are documented annually and over 1 million of those result in death. Plasmodium falciparum is the most lethal of five species known to infect humans. To further compound this problem, drug-resistant parasite strains have been documented for every currently available antimalarial drug, making the need to identify new drug targets more urgent than ever. Modern genetics have found that more than 50% of the Plasmodium genome codes for proteins of unknown functions, with no significant sequence homology to any known eukaryotic genes. Recent advances in forward genetics and the use of transposable elements to manipulate the genome of P. falciparum have made tremendous contributions to discovering the functions of these unknown genes, which is critical to rapidly advance antimalarial drug development. In this study we have identified a gene of unknown function, PF3D7_1143500, that is significant for intraerythrocytic development of Plasmodium. This gene exhibits weak similarities to the human regulator of chromatin condensation 1 protein (RCC1) and appears to belong to the class of RCC1-like proteins that perform diverse functions in eukaryotes. A thorough cellular and molecular analysis of an insertional knockout mutant of PF3D7_1143500 in P. falciparum has revealed a critical role for this gene in the production of merozoites during the intraerythrocytic cycle. The insertional mutant parasite strain displays a significant delay in initiating nuclear division, which results in a 40% reduction in the number of merozoites produced at the end of the intraerythrocytic cycle, thereby severely attenuating the parasite growth rate. PF3D7_1143500 localizes to the microtubule organization centers within the nucleus during the early stages of parasite development, suggesting it functions in regulating mitosis. Since cell cycle regulatory mechanisms are largely unknown in Plasmodium, the identification of this novel RCC1-like protein promises to offer new insights into this critical biological pathway that has high potential as an antimalarial drug target.

Download or read book The Malaria Genome Projects written by Irwin W. Sherman and published by World Scientific. This book was released on 2012 with total page 389 pages. Available in PDF, EPUB and Kindle. Book excerpt: The year 2012 marks the tenth anniversary of the announcement of the genome sequence of the human malaria parasite Plasmodium falciparum and that of its mosquito vector Anopheles. The genome sequences were a result of the Plasmodium falciparum Genome Project. This book covers in detail the biology of malaria parasites and the mosquitoes that transmit the disease, how the Genome Project came into being, the people who created it, and the cadre of scientists who are attempting to see the promise of the Project realized. The promise was: a more complete understanding of the genes of the parasite (and its vector) would provide a rational basis for the development of antimalarial drugs and vaccines, allow a better understanding of the regulation of the complex life cycle in the red blood and liver cells of the human, identify the genes the parasite uses to thwart the host immune response and the ways in which the parasite evades cure by drug treatments, as well as leading to more effective measures of control transmission. The hope was that cracking the genetic code of Plasmodium and Anopheles would reveal the biochemical Achilles heel of the parasite and its vector, leading to the development of novel drugs and better methods of control, and by finding the targets of protective immunity could result in the manufacture of effective vaccines. Through a historic approach, this book will allow for those new to the field, or those with insufficient background in the sciences, to have an easier entry point. Even scientists already working in the field may better appreciate how discoveries made in the past can impact the direction of future research.

Download or read book DNA Sequence Context and the Chromatin Landscape Differentiate Sequence specific Transcription Factor Binding in the Human Malaria Parasite Plasmodium Falciparum written by Victoria Bonnell and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria, caused by protozoan parasites of the genus Plasmodium, remains a major global health burden, with 247 million cases and killing 619,000 in 2021 alone. In Plasmodium falciparum, the deadliest human malaria parasite, about 90% of the protein-coding genes are transcribed in a periodic fashion over the 48-hour intraerythrocytic development cycle (IDC), with the peak transcript abundance generally occurring just before the protein is required. The periodicity of transcription forms a genome-wide cascade of continuous gene expression, which is believed to be finely regulated by a limited number of transcriptional regulators, including the 30-member Apicomplexan APETALA2 (ApiAP2) family of sequence-specific transcription factors (TFs). Interestingly, this family of proteins has AP2 DNA-binding domains only evolutionarily conserved in plant-linage genomes and Apicomplexan parasites, making them potential drug targets for novel antimalarial therapeutics in humans. The current literature is focused only on identifying regulatory networks controlled by the ApiAP2 TFs; however, dissecting the molecular mechanisms of their genome-wide binding pattern is still understudied. Knowing mechanisms of binding site selection of putative drug targets is critical to identifying essential interactions or features to be blocked. This dissertation elucidates the biological function and binding specificity of a subset of ApiAP2 TFs, which each recognize similar DNA sequence motifs in vitro, along with their chromatin-remodeling interaction partners. This project applies in vitro, in vivo, and in silico approaches to identify how sequence preferences are established during parasite development by probing the effects of cis- and trans- regulation on TF binding, in addition to dissecting the function of these TFs in parasite development. In higher eukaryotes, TFs with similar binding preferences can carry out different regulatory functions in a given cell type, work synergistically or antagonistically, perform similar functions in different cell types, or can be fully redundant and only necessary in the event that the primary factor cannot function. The occurrence of multiple TFs recognizing similar DNA sequence motifs in P. falciparum is intriguing since functional gene redundancy is not often evolutionarily conserved in pathogens. Therefore, despite the similar DNA binding motifs of these proteins, we predict that they carry out distinct regulatory functions in the parasite. There are several established features investigated by this work that can modulate binding specificity of a TF such as: DNA sequence context/intrinsic DNA shape, interaction with cofactors, histone post-translational modification, and chromatin accessibility. It is critical to understand which features, or combinations thereof, influence binding specificity of transcriptional regulators in P. falciparum to inform future antimalarial drug development.

Download or read book Malaria Parasites written by Andrew P. Waters and published by Caister Academic Press Limited. This book was released on 2004 with total page 578 pages. Available in PDF, EPUB and Kindle. Book excerpt: The completion of the Plasmodium falciparum genome sequence in late 2002 heralded a new era in malaria research. The search began in earnest for new drugs and vaccines to combat malaria, a disease which afflicts up to 500 million people worldwide and is responsible for the deaths of more than one million people each year. The new genomic data is aiding a greater understanding of the living parasite and its interaction with the insect vector and human host. In this book internationally renowned experts provide up-to-date reviews of the most important aspects of post-genomic malaria research. Topics covered include: the P. falciparum genome and model parasites, bioinformatics and genome databases, microsatellite analysis, analysis of chromosome structure, cell cycle to RNA polymerase I and II mediated gene expression, role of the nuclear genome, the parasite surface and cell biology, and much more. The book is essential to all researchers working in this highly topical field and is recommended reading for scientists in other areas of biology and medicine.

Download or read book Functional Characterization of a Puf Protein Family Member in Malaria Parasite Plasmodium Falciparum written by Xiaoying Liang and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Regulation of gene expression is important to cellular growth and differentiation of eukaryotes, as it plays key roles in determining the eventual expression levels and cellular localizations of a large number of proteins. RNA-binding proteins (RBPs) with conserved RNA-binding domains (RBDs) are key molecules in controlling gene expression. These conserved RBDs can specifically interact with target RNAs through specific sequences and structures to regulate mRNA stability, translation efficiency and subcellular localization. One of the well-studied RBPs is the Puf family RBPs. Members of the Puf family share a highly conserved Puf RBD, which typically consists of eight imperfect tandem repeats of ~36 amino acids (aa). Here I report the studies of two Puf members, PfPuf3 in Plasmodium falciparum and its ortholog PyPuf3 in Plasmodium yoelii. Both genes could not be disrupted, suggesting that they may be essential for the intraerythrocytic developmental cycle (IDC). A time-course study of both PfPuf3 mRNA and protein indicated that PfPuf3 was expressed during the entire IDC, with peak expression in early trophozoites. Cellular fractionation demonstrated that PfPuf3 preferentially partitioned to the nuclear than the cytoplasmic fractions. Interestingly, tagging of the endogenous of PfPuf3 and PyPuf3 with the green fluorescent protein showed that both proteins were limited to the nucleus, which is in contrast to the cytoplasmic localization of PfPuf1 and PfPuf2. Further, we found PfPuf3 co-localized with a well-known nucleolus maker PfNop1, demonstrating that PfPuf3 is a nucleolar protein. Using a parasite line with PfPuf3-tagged with PTP (ProtC-TEV-ProtA), we were able to affinity purify the PfPuf3 protein complex and the associated RNAs. Proteomic analysis of the PfPuf3 complex identified 32 proteins that are associated with the 60S ribosome subunit, suggesting that PfPuf3 might be involved in ribosomal biogenesis. RNA sequencing analysis of the purified PfPuf3 complex revealed significant enrichment of the 28S rRNA and ITS2 (internal transcribed spacer 2), implying that PfPuf3 may recognize and bind to these rRNA sequences. Taken together, these results demonstrated nucleolar localization of PfPuf3 and suggested an essential function of PfPuf3 in ribosomal biogenesis.

Download or read book Functional Investigation of Unknown Malaria Proteins in the Human Malaria Parasite Plasmodium Falciparum written by Marius Florian Schmitt and published by . This book was released on 2020 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Integrative Transcriptome and Phenome Analysis Reveals Unique Regulatory Cascades Controlling the Intraerythrocytic Asexual and Sexual Development of Human Malaria Parasites written by RieÌ8tte Andele̹ Van Biljon and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Plasmodium falciparum parasite, the major causative agent of malaria on the African continent, has evolved numerous cellular adaptations to effectively propagate its species. The parasite can proliferate asexually, producing mass amounts of progeny to subsist in the human host or differentiate into sexual forms (gametocytes) that, once mature, can transmit to a feeding Anopheles mosquito. Key to our ability to effectively develop chemical candidates that interfere with either of these processes is the identification and understanding of critical factors that regulate parasite development. This is particularly true for the development of antimalarials that can be used in malaria elimination strategies by targeting both parasite proliferation and transmission. We therefore hypothesized that parasite proliferation and differentiation use divergent mechanisms for gene expression that could be observed through a thorough investigation of the functional genome of these different parasite forms. This doctoral study therefore set out to increase our knowledge base on three crucial aspects of parasite development: 1) the atypical cell cycle that allows the rapid proliferation of asexual parasites; 2) the full molecular profile of gametocytogenesis enabling the cellular differentiation that allows the parasite to transmit; and 3) the metabolic differences between these proliferating and differentiating parasites that results from their strategy-specific mechanisms of developmental control. The atypical cell cycle of the parasite, associated with the massive cell number expansion in asexual development, is notoriously difficult to study. Here, we contributed a novel system by developing a cell cycle synchronization tool that reversibly blocks the development of asexual parasites at the G1/S transition. This results in an inescapable arrest of the cell cycle that is completely and functionally reversible; parasites re-initiate cell cycle progression and continue to S phase within 6 h. This system provided the opportunity to characterize cell cycle phases in the parasite and additionally evaluate molecular mechanisms associated with cell cycle arrest or re-initiation. During cell cycle arrest, the parasite enters a quiescent state reminiscent of a mitogen-activated restriction point. This arrest is unique and solely attributed to the removal of the specific mitogens within this system, polyamines. These analyses indicate the close interaction between transcriptional regulation and signal transduction cascades in the progression through the parasite℗þs cell cycle and for the first time highlight aspects of controlled cell cycle regulation in Plasmodium. In contrast to proliferation, the process of sexual differentiation only started receiving attention in the past few years. As such, we lack fundamental understanding of the mechanisms driving the unique gametocyte differentiation of P. falciparum parasites. This study contributes a detailed analysis of gametocyte differentiation that revealed distinct developmental transitions demarcating the start of gametocytogenesis, intermediate gametocyte development and finally maturation to produce the transmissible mature gametocytes. The study provides evidence for coordinated regulation of gene expression on a transcriptional level. We propose a model for regulation of gametocytogenesis in malaria parasites that involves active repression of gene sets mediated through epigenetics and RNA destabilization as well as active transcription of gene sets through successive ApiAP2 transcription factor activity. This data provides the most detailed framework of coordinated gene regulation events underlying development of P. falciparum gametocytes to date, a unique resource for the malaria community. The comprehensive and complex transcriptional regulation described for the proliferation and differentiation of the parasite led us to evaluate the functional consequence thereof. A whole cell phenotype microarray system was evaluated for its ability to measure the metabolic processes that define asexual and sexual stage metabolism as a functional consequence of changed gene expression profiles during proliferation and differentiation. The study provided metabolic profiles detailing carbon and nitrogen metabolism in asexual parasites, mature and immature gametocyte stages. The data highlighted dipeptide metabolism as a distinguishing feature in mature gametocytes and showed the presence of a low, delayed metabolic state concurrent with reduced transcriptional activity observed in this stage. These results show that gene expression changes associated with differentiation compared to proliferation translate to an observable metabolic phenotype and that transcriptional regulation shapes the molecular landscape underlying crucial events that enable the parasite℗þs intraerythrocytic asexual and sexual development.

Download or read book A Genetic Analysis to Elucidate the Function of the Plasmodium Falciparum Parasitophorous Vacuole Protein PfPV1 written by and published by . This book was released on 2009 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is one of the most lethal infectious diseases worldwide. Understanding the biology of the causative agent Plasmodium will lead to better control of the disease. The biogenesis and maintenance of the parasitophorous vacuole (PV) within the infected erythrocyte is an essential factor for parasite survival. The PV has been postulated to be involved in various pivotal functions, however little is known about the PV contents and their respective functions. Our group had previously provided the first PV's proteome research and have continuously exposed more members of this important compartment. The protein PfPV1 was a newly discovered PV localisation protein, encoded by the PF11_0302 gene. In order to address the function of this protein a gene knock-out strategy was applied. A search for the interacting proteins of PfPV1 was also carried out using the GST pull-down assay. The first attempt to knock out the encoding gene was the double-crossover strategy in the presence of a negative selection. The knocked-out parasite was unable to obtain. However, the integration into the PfPV1 locus did occur, evidenced by the presence of both endogenous and knock-out band in the specific southern blot hybridisation. The PfPV1 gene was therefore assumed to be essential for in vitro growth, thus the targeting into the endogenous locus was accompanied by a duplication event for maintaining expression of the gene. The assumption was further validated by the second knock-out strategy, using the complementing experiment. The result had been expected to be able to disrupt the endogenous gene locus through the knock-out vector while concomitantly expressing a copy of PfPV1 under the control of a foreign promoter from an episomal plasmid, which should not recombine with the endogenous gene locus. However, the gene was still resistant to be disrupted. Various clones were isolated from the double transfected parasites. One of the clones has lost the episomal copy of the PfPV1 gene and s.

Download or read book Understanding Phospholipid Biosynthesis in the Human Malaria Parasite Plasmodium Falciparum Using Saccharomyces Cerevisiae as a Surrogate System written by Teresa C. Santiago and published by . This book was released on 2005 with total page 346 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 Investigating the Druggability and Biological Roles of Apicomplexan AP2 Transcription Factors in the Human Malaria Parasite Plasmodium Falciparum written by Timothy Russell and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Plasmodium falciparum, the most virulent of the human infectious malaria parasites, caused over 600,000 deaths in 2020. Alarmingly, malaria deaths have increased since 2019 and resistance has been reported for every antimalarial drug deployed to date. Regulation of gene expression is critical for P. falciparum to complete its complex life cycle, which includes stages in the human host and Anopheles mosquito vector. Gene regulation in malaria parasites is primarily driven by the Apicomplexan AP2 (ApiAP2) proteins, a single expanded family of sequence specific DNA binding transcription factors. ApiAP2 proteins are plant derived and therefore have no homologs encoded in the human or mosquito genomes, making them potential drug targets. In order to exploit ApiAP2 proteins as antimalarial intervention targets, it is important to both identify ApiAP2 inhibitors and to probe the biological function of ApiAP2 proteins. In this thesis work, ApiAP2 proteins have been investigated to assess their biological functions and druggability. In Chapter 2, putative competitors of DNA binding by the ApiAP2 protein AP2-EXP were selected using an in silico screen. Several compounds were found to inhibit ApiAP2 DNA binding in vitro using DNA gel-shifts. An ApiAP2 competitor compound was then leveraged for use as a chemical genetic tool to interrogate the function of AP2-EXP. In Chapter 3, a potential cooperative interaction between the ApiAP2 proteins PfAP2-I and PfAP2-G during P. falciparum sexual development was interrogated by mapping the DNA binding occupancy of each protein. PfAP2-I genomic occupancy changes in the presence of PfAP2-G, indicating for the first time a causal relationship between two P. falciparum transcription factors that regulates DNA binding specificity. PfAP2-I and PfAP2-G co-occupancy coincides with the activation of P. falciparum sexual stage genes. In Chapter 4, the first indications of the gene regulatory functions of the ApiAP2 proteins PfAP2-HS and PfAP2-O3 were uncovered by mapping their genome-wide DNA binding occupancies. PfAP2-HS was found to regulate a transcription program that is required for P. falciparum to survive febrile host temperatures, while PfAP2-O3 primarily occupies the gene bodies of loci encoding tRNA and rRNA during sexual development. In aggregate, this thesis work describes efforts to further understand the unique ApiAP2 transcription factor proteins in the human malaria parasite P. falciparum.

Download or read book Integrative Transcriptome and Phenome Analysis Reveals Unique Regulatory Cascades Controlling the Intraerythrocytic Asexual and Sexual Development of Human Malaria Parasites written by Ri tte Andel Van Biljon and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The Plasmodium falciparum parasite, the major causative agent of malaria on the African continent, has evolved numerous cellular adaptations to effectively propagate its species. The parasite can proliferate asexually, producing mass amounts of progeny to subsist in the human host or differentiate into sexual forms (gametocytes) that, once mature, can transmit to a feeding Anopheles mosquito. Key to our ability to effectively develop chemical candidates that interfere with either of these processes is the identification and understanding of critical factors that regulate parasite development. This is particularly true for the development of antimalarials that can be used in malaria elimination strategies by targeting both parasite proliferation and transmission. We therefore hypothesized that parasite proliferation and differentiation use divergent mechanisms for gene expression that could be observed through a thorough investigation of the functional genome of these different parasite forms. This doctoral study therefore set out to increase our knowledge base on three crucial aspects of parasite development: 1) the atypical cell cycle that allows the rapid proliferation of asexual parasites; 2) the full molecular profile of gametocytogenesis enabling the cellular differentiation that allows the parasite to transmit; and 3) the metabolic differences between these proliferating and differentiating parasites that results from their strategy-specific mechanisms of developmental control. The atypical cell cycle of the parasite, associated with the massive cell number expansion in asexual development, is notoriously difficult to study. Here, we contributed a novel system by developing a cell cycle synchronization tool that reversibly blocks the development of asexual parasites at the G1/S transition. This results in an inescapable arrest of the cell cycle that is completely and functionally reversible; parasites re-initiate cell cycle progression and continue to S phase within 6 h. This system provided the opportunity to characterize cell cycle phases in the parasite and additionally evaluate molecular mechanisms associated with cell cycle arrest or re-initiation. During cell cycle arrest, the parasite enters a quiescent state reminiscent of a mitogen-activated restriction point. This arrest is unique and solely attributed to the removal of the specific mitogens within this system, polyamines. These analyses indicate the close interaction between transcriptional regulation and signal transduction cascades in the progression through the parasite s cell cycle and for the first time highlight aspects of controlled cell cycle regulation in Plasmodium. In contrast to proliferation, the process of sexual differentiation only started receiving attention in the past few years. As such, we lack fundamental understanding of the mechanisms driving the unique gametocyte differentiation of P. falciparum parasites. This study contributes a detailed analysis of gametocyte differentiation that revealed distinct developmental transitions demarcating the start of gametocytogenesis, intermediate gametocyte development and finally maturation to produce the transmissible mature gametocytes. The study provides evidence for coordinated regulation of gene expression on a transcriptional level. We propose a model for regulation of gametocytogenesis in malaria parasites that involves active repression of gene sets mediated through epigenetics and RNA destabilization as well as active transcription of gene sets through successive ApiAP2 transcription factor activity. This data provides the most detailed framework of coordinated gene regulation events underlying development of P. falciparum gametocytes to date, a unique resource for the malaria community. The comprehensive and complex transcriptional regulation described for the proliferation and differentiation of the parasite led us to evaluate the functional consequence thereof. A whole cell phenotype microarray system was evaluated for its ability to measure the metabolic processes that define asexual and sexual stage metabolism as a functional consequence of changed gene expression profiles during proliferation and differentiation. The study provided metabolic profiles detailing carbon and nitrogen metabolism in asexual parasites, mature and immature gametocyte stages. The data highlighted dipeptide metabolism as a distinguishing feature in mature gametocytes and showed the presence of a low, delayed metabolic state concurrent with reduced transcriptional activity observed in this stage. These results show that gene expression changes associated with differentiation compared to proliferation translate to an observable metabolic phenotype and that transcriptional regulation shapes the molecular landscape underlying crucial events that enable the parasite s intraerythrocytic asexual and sexual development.