Vacancies

Currently available: Two postdoctoral Fellowships, at the Universidad Nacional de Rosario, Argentina (closing dates 25th February 2019 and 1st March 2019); Three PhD positions at Durham University, UK 
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Postdoctoral fellowship: Heme homoeostasis in Trypanosoma cruzi as a target to inhibit parasite proliferation

Project supervisor: Julia A. Cricco (IBR-CONICET, Universidad Nacional de Rosario)

Co-supervisors: Carlos Robello (Fac. de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario)

Ehmke Pohl (University of Durham, UK)

Pamela Cribb (IBR-CONICET, Universidad Nacional de Rosario)

Pablo Armas (IBR-CONICET, Universidad Nacional de Rosario)








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Based at: IBR Instituto de Biología Molecular y Celular de Rosario. Fac. de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario. Laboratorio de Biología y Bioquímica del Trypanosoma cruzi (http://www.ibr-conicet.gov.ar/laboratorios/serra/). Rosario, Santa Fe. Argentina

Stipend: Equivalent to CONICET postdoctoral fellowship; transportation and installation expenses are not included

Starting: April 1st, 2019 for 24 months

Closing date: February 25th, 2019

Project Description

Trypanosoma cruzi is a parasite that causes Chagas disease, the most relevant parasitic disease in several South American countries, and which has become a relevant health problem in many non-endemic countries through migration of infected individuals and spread of its insect vector, the ‘kissing bug’.

T. cruzi, as well as other trypanosomatids relevant for human health, rely upon their hosts to supply essential metabolites and cofactors. These parasites do not produce heme, but they have several heme proteins involved in essential metabolic pathways. T. cruzi is able to import heme from its hosts during the replicative stages; the protein TcHTE is essential for this heme transport activity. Heme is also a highly toxic molecule, meaning that the parasite must strictly control its heme homeostatic processes (importation, trafficking and detoxification) where TcHTE and other unknown proteins are directly involved.

The aim of this project is to elucidate the molecular mechanisms for heme homeostasis. Considering that known heme chaperones, transporters and detoxifying enzymes have not been yet identified in T. cruzi, the project would identify the novel proteins fulfilling these essential roles, and which may prove suitable as new targets for new drug development against Chagas disease.

References:


  • Tripodi KEJ, Menendez Bravo SM, Cricco JA. Role of heme and heme-proteins in trypanosomatid essential metabolic pathways. Enzyme Res 2011; 2011: 873230.

  • Merli ML, Pagura L, Hernández J, Barisón MJ, Pral MF, Silber AM, et al. The Trypanosoma cruzi Protein TcHTE Is Critical for Heme Uptake. PLoS Negl Trop Dis 2016;1–18.

  • Merli ML, Cirulli BA, Menendez-Bravo SM, Cricco JA. Heme A synthesis and CcO activity are essential for Trypanosoma cruzi infectivity and replication. Biochem J England 2017; 474: 2315–2332.


Keywords

Heme transport, heme homeostasis, drug targets, Chagas disease, neglected tropical diseases

Eligibility

Applicants require a PhD in Biological Sciences or similar (to be completed by March 31st, 2019) and experience in one or more of the following: microbiology, molecular biology or parasitology, along with excellent written and spoken English.

How to apply

Interested applicants should send a full CV, a covering letter and 2 (two) references, to Julia Cricco (cricco@ibr-conicet.gov.ar)

Postdoctoral fellowship: Antibiotic-inspired, activity-based probes for serine proteases profiling in Trypanosoma cruzi

Project supervisor: Guille Labadie (Fac. de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario)

Co-supervisorsPatrick Steel (University of Durham, UK)

Julia A. Cricco (IBR-CONICET, Universidad Nacional de Rosario)

Iqbal Choudhary (University of Karachi, Pakistan)








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Based at: Department of Organic Chemistry, Fac. de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario. Rosario, Santa Fe. Argentina.

Stipend: Equivalent to CONICET postdoctoral fellowship; transportation and installation expenses are not included

Starting: April 1st, 2019 for 24 months

Closing date: March 1st, 2019

Project Description

There are between 6 to 7 million people infected worldwide with Trypanosoma cruzi, the parasite that causes Chagas disease, principally in Latin America but the disease is spreading to other continents. Benznidazole and nifurtimox are the approved drugs for treatment of T. cruzi infection, but are only effective against the acute form of the disease, and their efficacy varies according to the drug susceptibility of different parasite strains. This treatment scenario, together with natural resistance in some strains to both drugs, underpins the urgent need to develop new anti-T. cruzi drugs.

A critical step in the new drug-development pipeline is the discovery and validation of well-characterized targets. This project offers an opportunity to develop a set of chemical probes, and use these to identify new T. cruzi proteins as putative drug targets. These probes will contain irreversible inhibitors attached to a detectable or handle group, allowing protein target identification, isolation and purification.

Serine proteases have been indicated previously as potential drug targets in T. cruzi, but not systematically studied in trypanosomatids. Using b-lactam antibiotics as warheads for activity-based probes, we will identify and validate new T. cruzi serine proteases as new drug targets, enabling the initiation of novel drug development programmes within the wider NTD Network membership.

Keywords

Chemical probes, activity-based probes (ABPs), serine proteases, drug targets, Chagas disease, neglected tropical diseases

Eligibility

Applicants require a PhD in Chemistry or similar (to be completed by March 31st, 2019) and experience in one or more of the following; synthetic organic chemistry, solid phase synthesis, and parasitology, along with excellent written and spoken English.

How to apply

Interested applicants should send a full CV, a covering letter and 2 (two) references, to Dr Carina Delpiccolo (delpiccolo@iquir-conicet.gov.ar) and/or Dr Agustina La Venia (lavenia@iquir-conicet.gov.ar).

PhD Studentship: New chemical tools to identify and validate drug targets in Leishmania and related protozoan parasites

Project Supervisor: Prof. Patrick Steel


 



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Durham University, Department of Chemistry/Department of Bioscience

Full time: 39 months, £14,777 per annum

Applications welcome from UK and International students

Starting: October 2019

Closing date: Applications will remain open until a suitable candidate is appointed

Project Description

This project will design, synthesise and apply new small molecule probes to enable an exploration of the druggable protein in Leishmania and related protozoan parasites (Trypanosoma cruzi & Trypanosoma brucei). These new compounds will either possess latent reactivity allowing them to be used as activity based enzyme (activated) labelling agents, as probes for post-translation modification related to parasite viability, or as switches for protein degradation with a view to isolating and characterising new and exciting targets.

The project will involve organic synthesis, molecular parasitology, structural biology and molecular biology techniques.  It is not expected that you will have experience of all these activities prior to commencing their studies, but a willingness to learn these and other new techniques is essential.

Keywords – organic synthesis, chemical biology, chemical probes, neglected tropical diseases

Eligibility

Applicants require an undergraduate degree at a 2:1 honours level or above (or equivalent) in a discipline directly relevant to the research areas of chemistry and biology.

The position is open to both UK and International students.

Applications

Interested applicants should send a CV (no longer than 2 pages, and should include the contact details of 2 referees) and a short cover letter to Prof. Patrick Steel (p.g.steel@durham.ac.uk)

PhD Studentship: Discovering new drug targets in the Sphingolipid biosynthesis pathway of protozoan parasites

Project Supervisors: Dr. Ehmke Pohl, Dr. Paul Denny


 



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Durham University, Department of Chemistry/Department of Bioscience

Full time: 39 months, £14,777 per annum

Applications welcome from UK and International students

Starting: October 2019

Closing date: Applications will remain open until a suitable candidate is appointed

Project Description

Protozoan parasites are a diverse group of pathogens responsible for diseases ranging from Malaria (Plasmodium spp.) and Toxoplasmosis (Toxoplasma gondii) to the neglected tropical diseases leishmaniasis (Leishmania spp) and Chagas disease (Trypanosoma cruzi).  In spite of considerable efforts over the last decade, treatment options remain limited.

Recently, we have identified enzymes involved in the sphingolipid biosynthesis as potential novel drug targets (Norcliffe et al. Sci Rep 2018; 8: 3938; Mina JG, et al. J Biol Chem 2017; 292(29):12208-12219.).  The aim of this project is to characterize these enzymes from different species by biochemical, biophysical and structural methods, ranging from X-ray crystallography to small angle X-ray scattering and Cryo-Electron Microscopy.

The successful candidate will be based in Durham, with opportunities for placement with our GCRF partners in Kolkata and/or Rio de Janeiro.

Keywords – structural biology, chemical biology, neglected tropical diseases

Eligibility

Applicants require an undergraduate degree at a 2:1 honours level or above (or equivalent) in a discipline directly relevant to the research areas of chemistry and biology. The position is open to both UK and International students.

Applications

Interested applicants should send a CV (no longer than 2 pages, and should include the contact details of 2 references) and a short cover letter to Dr. Ehmke Pohl (Ehmke.pohl@durham.ac.uk, or on twitter @ehmke_pohl

PhD Studentship: The development of new peptide and peptoid based treatments for Neglected Tropical Diseases (NTDs)

Project Supervisor: Associate Prof. Steven Cobb


 



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Durham University, Department of Chemistry

Full time: 39 months, £14,777 per annum

Applications welcome from UK and International students

Starting: October 2019

Closing date: Applications will remain open until a suitable candidate is appointed

Project Description

Neglected tropical diseases (NTDs) are a significant global health burden, affecting approximately one-sixth of the world’s population. The illnesses classified as NTDs by the World Health Organization (WHO) include conditions that have historically been overlooked by international public health efforts, leading to insufficient prevention and treatment options. These diseases are typically endemic inEligibility resource-poor, developing countries where populations have limited access to healthcare, and a lack of resources to tackle the disease. NTDs such as leishmaniasis and Chagas disease are infections caused by insect vector-borne protozoan parasites. Combined, these vector-borne diseases affect some of the world’s poorest communities, particularly in tropical and sub-tropical regions. In addition to the mortality of these diseases, they can cause severe disfigurement or long-term disability leading to significant social and economic consequences.

The PhD project will build on our previous work in the area of leishmaniasis [see Cobb, et al. J Pept Sci 2011; 17: 75; Molecules, 2015, 20, 2775; Chem Med Chem 2015; 10: 233 and Med Chem Comm 2016; 7: 799] and will also involve a new collaboration with Professor Ariel Silber (expert in Chagas disease, University of São Paulo, Brazil).  The project will adopt both chemical and biological tools to elucidate the mode of action by which previously identified peptides and peptoids function with the view to validating new drug targets for the treatment of both leishmanaisis and Chagas disease. The successful candidate will receive training in a range of both chemical and biological techniques and whilst the project will be based in Durham, aspects of the work will be carried out via a secondment in the Silber laboratory in Brazil.

Keywords – organic synthesis, peptide chemistry, chemical-biology, neglected tropical diseases

Eligibility

Applicants require an undergraduate degree at a 2:1 honours level or above (or equivalent) in a discipline directly relevant to the research areas of chemistry and biology. The position is open to both UK and International students.

Applications

Interested applicants should send a CV (no longer than 2 pages, and should include the contact details of 2 references) and a short cover letter to Steven Cobb (Email – s.l.cobb@durham.ac.uk)