The VALIDATE Network - Vaccine development for complex intracellular neglected pathogens
Postdoctoral Scholarships - The UK:Brazil Joint Centre Partnership in Leishmaniasis (JCPiL), 2019
Deadline date for applications: 25 Oct 2019
There are 4 postdoctoral scholarships available to develop the projects in the laboratories of Angela Kaysel Cruz, Dario Zamboni, Hiro Goto and Luiz Tosi.
Project: Epigenetic regulation of Leishmania gene expression
PI: Angela Kaysel Cruz
Summary: Leishmania gene expression control occurs mainly at the posttranscriptional level. At the centre of the regulatory complexes are cis- and transregulatory elements, mainly represented by mRNA elements (cis-elements) and RNA binding proteins (RBPs) which may well include a thus-far unexplored content of noncoding transcripts (ncRNAs), recently detected in these parasites. Cruz and co-workers have demonstrated that ncRNAs seems to be a common feature of Leishmania transcriptomes and hundreds of putative ncRNAs were identified as differentially expressed (DE) transcripts. The DE L. braziliensis ncRNAs and interacting RBPs will be functionally investigated. The post-doctoral fellow will use state of the art technologies for genome editing to generate knockout (KO) of DE ncRNAs in L. braziliensis and to endogenously tag these ncRNAs to evaluate phenotypic changes and identify interacting partners. The post-doctoral fellow from the Brazilian laboratory will be engaged in the complementary studies to be developed in the UoY, under the guidance of M
Project: The inflammasome in response to L. infantum infection in mouse models of infection
PI: Dario Zamboni
Summary: Leishmaniasis is a complex infectious disease highly important in tropical and subtropical regions in the world. The main focus of the lab is the investigation of the interactions of intracellular pathogens with host cells, a multidisciplinary area of research involving Immunology, Cell Biology and Microbiology. The selected candidate will investigate how the immune system senses Leishmania infantum parasites and operate to clear infection and how these parasites subvert the host cell functions to replicate intracellularly and cause systemic disease. To achieve these goals, we use modern tools of molecular biology, biochemistry, and genetics.
Project: Molecular pathology of leishmaniasis:towards host-directed therapy in leishmaniases
PI: Hiro Goto
Summary: The leishmaniases are parasitic diseases caused by one of several species of single cell parasites (Leishmania) that are transmitted to humans by the bite of infected sand flies. These diseases affect over 150 million people across 98 countries worldwide. Some forms of leishmaniasis are fatal, whereas other are very stigmatising and affect quality of life. Few drugs are available for patients and no vaccines are currently registered for use in preventing or treating these diseases. Importantly, the drugs that we do have are not universally effective and often have significant side effects. Sometimes patients even in the same geographical area will respond quite differently to therapy. In this proposal, we will use new molecular approaches to perform deep phenotyping on tissue samples collected from patients with various forms of leishmaniasis to analyse cellular and molecular elements engaged in pathogenesis and treatment response. The aim is to identify host and parasite targets that could be the focus for developing novel therapies.
Project: Does signaling during DNA replication stress drive genome diversity in Leishmania?
PI: Luiz Tosi
Summary: The genome of Leishmania is characterized by a remarkable plasticity that has been associated with the acquisition of drug resistance and with host adaptation. Here, we will explore if the parasite’s signaling of replication ‘stress’ may underlie genome plasticity and diversity. The analysis of the ATR pathway, which is central to the detection and signaling DNA replication stress and damage, is key to understand the above questions. To date, there has been greater characterization of the Leishmania 9-1-1 complex, which is a key element at the early steps of the pathway. The main goal of this proposal is to extend the characterization of the ATR pathway and explore the structure and function of other key components of this orchestrated response.
To find out more, or how to apply, visit the job webpage.