Johannes Sebastian Paul Doehl

Pós-doutorado

Idiomas

Participação em eventos

Produções bibliográficas

• DOEHL, JOHANNES S. P. ; SÁDLOVÁ, JOVANA ; ASLAN, HAMIDE ; PRU'INOVÁ, KATE'INA ; METANGMO, SONIA ; VOTÝPKA, JAN ; KAMHAWI, SHADEN ; VOLF, PETR ; SMITH, DEBORAH F. . Leishmania HASP and SHERP Genes Are Required for In Vivo Differentiation, Parasite Transmission and Virulence Attenuation in the Host. PLoS Pathogens (Online) , v. 13, p. e1006130, 2017.

• PRICE, HELEN P. ; PAAPE, DANIEL ; HODGKINSON, MICHAEL R. ; FARRANT, KATIE ; DOEHL, JOHANNES ; STARK, MEG ; SMITH, DEBORAH F. . The -BBSome subunit BBS1 is essential for parasite virulence in the mammalian host. Molecular Microbiology (Print) , v. 90, p. 597-611, 2013.

Projetos de pesquisa

• 2013 - Atual

  The mammalian immune system in the transmission of L. (L.) donovani from a chronically infected mammalian host to the sand fly vector, Descrição: Investigação no papel do sistema imunológica do mamífero na transmissão L. (L.) donovani LV9, causador da leishmaniose visceral, aos flebotomíneos. Considerando, que a maioria de parasitas na infecção visceral esta residente nos tecidos profundos como o baço, o fígado e a medula óssea e que a presença de parasitas eh bem variável no sangue dependendo da linhagem de parasita e do hospedeiro, eh difícil de determinar como L. (L.) donovani consegue ser transmitido aos flebotomíneos. Existe a possibilidade que o sistema imunológica do hospedeiro leva parasitas ao pele em macrófagos infectados por respostas inflamatórias. Alem disso estamos tentando de estabelecer a frequência com que flebotominoes conseguem ser infetado pela alimentação de sangue dia mamífero infectado. Também estou investigando a distribuição de parasitas no pele de um hospedeiro infectado cronicamente com L. (L.) donovani. A pesquisa quer idenficar novas aplicações para uma vacina terapêutico contra a Leishmania que esta desenvolvido no meu grupo, para diminuir a possibildade de transmissão da Leishmania ao vetor.. , Situação: Em andamento; Natureza: Pesquisa. , Integrantes: Johannes Sebastian Paul Doehl - Coordenador / Paul M. Kaye - Integrante / Najmeeyah Brown - Integrante / Jane Dalton - Integrante.

• 2009 - Atual

  Investigating the role of the Leishmania (Leishmania) major HASP and SHERP genes during metacyclogenesis in the sand fly vectors, Phlebotomus (Phlebotomus) papatasi and Ph. (Ph.) duboscqi, Descrição: Leishmania parasites are the causative agents of a diverse spectrum of infectious diseases termed the leishmaniases. These digenetic parasites exist as intracellular, aflagellate amastigotes in a mammalian host and as extracellular flagellated promastigotes within phlebotomine sand fly vectors of the family Phlebotominae. Within the sand fly vector?s midgut, Leishmania has to undergo a complex differentiation process, termed metacyclogenesis, to transform from non-infective procyclic promastigotes into mammalian-infective metacyclics. Members of our research group have shown previously that parasites deleted for the L. (L.) major cDNA16 locus (a region of chromosome 23 that codes for the stage-regulated HASP and SHERP proteins) do not complete metacyclogenesis in the sand fly midgut, although metacyclic-like stages can be generated in in vitro culture (Sádlová et al. Cell. Micro.2010, 12, 1765-79). To determine the contribution of individual genes in the locus to this phenotype, I have generated a range of 17 mutants in which target HASP and SHERP genes are reintroduced either individually or in combination into their original genomic locations within the L. (L.) major cDNA16 double deletion mutant. All replacement strains have been characterized in vitro with respect to their gene copy number, correct gene integration and stage-regulated protein expression, prior to phenotypic analysis. HASPA1 was not detected in cultured promastigotes, but was expressed in mouse isolated amastigotes. Parasite mutant lines were passaged through susceptible BALB/c mice, during which HASPA2 gene containing mutant lines, in the absence of a HASPA1 gene, were shown not to develop lesions. Mouse-passaged parasites were used to infect the L. (L.) major specific sand fly vectors, Ph. (Ph.) papatasi and Ph. (Ph.) duboscqi. The progress of parasite metacyclogenesis was then monitored over twelve days, by midgut dissection and microscopy. Metacyclogenesis was not fully recovered in any of the replacement mutants tested. Surprisingly, HASPB protein expression could not be detected in the replacement mutants within the sand fly midgut, although HASPB protein was readily detected when the same parasite lines were cultured in vitro. The same was true for SHERP, although in situ expression was recovered in the presence of a HASPB gene, which itself did not expressed detectable HASPB protein levels. These observations suggest a requirement for one or multiple as-yet-unidentified regulatory component(s) for HASPB expression within the sand fly midgut and these are not required in culture. Quantitative PCR data suggested HASPB upregulation to be essential for metacyclogenesis completion, suggesting a sand fly specific function for HASPB.. , Situação: Em andamento; Natureza: Pesquisa. , Alunos envolvidos: Doutorado: (1) . , Integrantes: Johannes Sebastian Paul Doehl - Coordenador / Jovana Sádlová - Integrante / Hamide Aslan - Integrante / Jan Votýpka - Integrante / Shaden Kamhawi - Integrante / Petr Volf - Integrante / Deborah F. Smith - Integrante.

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