Lanzer, Michael

Untersuchungen zur Kompetition zwischen Repressor und RNA-Polymerase um DNA-Bindungsorte by Michael Lanzer( Book )

9 editions published between 1988 and 1989 in German and held by 22 WorldCat member libraries worldwide

Verbundprojekt: TTU 03.701 - Laboratory research group Translational Malaria Research (Ruprecht-Karls-Universität Heidelberg) Teilprojekte: TTU 03.701 - Laboratory research group Translational Malaria Research (Ruprecht-Karls-Universität Heidelberg) by Christian Epp( )

1 edition published in 2016 in German and held by 18 WorldCat member libraries worldwide

Verbundprojekt: TTU 03.901 - Regulatory preclinical studies and development of SC83288 as a novel antimalarial drug (Ruprecht-Karls-Universität Heidelberg) by Michael Lanzer( )

1 edition published in 2016 in German and held by 17 WorldCat member libraries worldwide

Verbundprojekt: TTU 03.803 - Preclinical development of SC83288 as a novel antimalarial drug candidate (Ruprecht-Karls-Universität Heidelberg) by Michael Lanzer( )

1 edition published in 2016 in German and held by 17 WorldCat member libraries worldwide

TTU 03.803 - Preclinical development of novel antimalarial drug candidates, with a focus on compounds that target PfATP6 Schlussbericht zum DZIF-Vorhaben by Michael Lanzer( )

1 edition published in 2019 in German and held by 10 WorldCat member libraries worldwide

Pathogen mimicry of eurkaryotic linear motifs by Hugo C Sámano-Sánchez( Book )

1 edition published in 2019 in English and held by 7 WorldCat member libraries worldwide

Structure-function analysis and membrane association of Leishmania tarentolae and Plasmodium falciparum Erv by Sandra Katharina Specht( )

2 editions published between 2018 and 2019 in English and held by 7 WorldCat member libraries worldwide

The RNAi-Competent Malaria Parasite: A Novel Strategy to Knock Down Plasmodium Genes via Non-Canonical RNAi by Franziska Hentzschel( )

3 editions published in 2017 in English and held by 6 WorldCat member libraries worldwide

Functional studies on the chloroquine resistance transporter (PfCRT) and the HECT E3 ubiquitin-protein ligase (PfUT) in Plasmodium falciparum by Monika Jankowska-Döllken( )

3 editions published in 2019 in English and held by 5 WorldCat member libraries worldwide

Posttranslational modifications (PTMs) affect fundamental cellular functions of the human malaria parasite Plasmodium falciparum, including regulation of protein stability, metabolism, proliferation, apoptosis and signal transduction. This study investigates the importance of phosphorylation and ubiquitination in modulating the parasite intraerythrocytic development, as well as their implication in antimalarial drug resistance. The chloroquine resistance transporter PfCRT is a drug-metabolite carrier annotated as a prominent determinant of parasite's reduced susceptibility to quinoline drugs. PfCRT is posttranslationally modified by phosphorylation and palmitoylation. However, the role of these PTMs in regulation of PfCRT function is not fully resolved. Chemical and genetic approaches employed in the current study revealed the relevance of PfCRT phosphorylation at serine 33 in regulating the drug resistance-mediating function of this transporter and in vitro fitness of the parasite. The PfCRT allelic exchange mutants, in which serine 33 was replaced by alanine showed increased sensitivity to chloroquine and quinine. Moreover, PfCRT serine 33 substitution by phospho-mimicking amino acids, glutamic and aspartic acid, could respectively partially and fully, restore the resistance phenotype. The fitness variation between the PfCRT mutants was linked to differences in merozoite numbers and their invasion efficiencies, with alanine mutants displaying a significant advantage in this regard. Identification of a kinase implicated in this phenomenon is desired, as its inhibition in combination with chloroquine could reduce or prevent the further spread of resistance. A HECT E3 ubiquitin ligase, termed ubiquitin transferase PfUT, is a novel candidate gene for multifactorial resistance to quinine. PfUT was shown to localize to the parasite's ER/Golgi complex, but its role in reduced susceptibility to quinine and its physiological function remain unclear. Characterization of PfUT was attempted by a glmS ribozyme-based conditional knockdown of encoding it gene, generated using the CRISPR-Cas9 genome editing technology. Unexpectedly, integration of the glmS sequence resulted in a 2-fold increase in PfUT transcripts correlated with protein levels. PfUT overexpression, in turn, led to S phase-associated lengthening of parasite's cycle, reflected in impaired growth. Glucosamine-induced incomplete downregulation partially restored the wild type phenotype. Moreover, the transgenic parasites exhibited an enhanced susceptibility to quinine and quinidine. An alternative disruption of the pfut locus via a selection-linked integration (SLI-TGD) strategy was unsuccessful, despite multiple attempts. These results underline the importance of PfUT in parasite proliferation and survival. However, a direct proof of PfUT's association with quinine resistance and identification of its biological substrates await further investigation

Role of Plasmodium falciparum transporters in drug resistance by Sonia Moliner Cubel( )

3 editions published in 2016 in English and held by 5 WorldCat member libraries worldwide