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Marie Curie INTEGRATE ETN announces 11 PhD student positions in antibacterial drug discovery

 
Applications are invited for 11 PhD student positions (“Early Stage Researchers”) to be funded by the Marie-Sklodowska-Curie Innovative Training Network “INTEGRATEInterdisciplinary Training Network for Validation of Gram-Negative Antibacterial Targets” within the Horizon 2020 Programme of the European Commission. INTEGRATE is a consortium of high profile universities, research institutions and companies located in Italy, Finland, Latvia, United Kingdom, Slovenia, Germany, Belgium and Portugal.
Number of positions available: 11 PhD student positions.
Career stage of applicants: Early Stage Researcher (ESR) or 0-4 yrs (Post Graduate)

Key dates:

9 March 2015: Deadline for on-line application for ESR positions (http://www.cdr.fi/news-and-events/integrate-etn-student-application-form)

27 March 2015: Communication list “preselected candidates”

5-6 May 2015: Recruitment Event (Verona) for preselected candidates

6 May 2015: Communication list “recruited INTEGRATE ESRs”

 

Benefits and salary

The MSCA programme offers highly competitive and attractive salary and working conditions. The successful candidates will receive a salary in accordance with the MSCA regulations for early stage researchers. Exact salary will be confirmed upon appointment [Living allowance = approximately 37.320 euro/year (depending on a correction factor to be applied per country) + Monthly mobility and family allowance = 600 or 1100 euro depending on the family situation]. In addition to their individual scientific projects, all fellows will benefit from further continuing education, which includes internships and secondments, a variety of training modules as well as transferable skills courses and active participation in workshops and conferences.
All applications must be submitted through the on-line job application form here. Candidates apply electronically for one to maximum three positions and indicate their preference. Candidates provide all requested information including a detailed CV. During registration, applicants will need to prove that they are eligible (three aspects: respect ESR definition, mobility criteria, English language proficiency). The deadline for the on-line registration is 9 March 2015. The INTEGRATE Recruitment Committee selects approximately 30 candidates for the Recruitment Event which will take place in Verona (5-6 May 2015). The selected candidates will provide a 15-minute presentation and will be interviewed by the Recruitment Committee. In order to facilitate their travel, selected candidates (if outside Italy) will receive a fixed, lump sum of 250 euro. The final selection of INTEGRATE PhD students will be communicated the day after the Recruitment Event. The selected ESRs are to start as quickly as possible (in practice: target 1 July 2015).

Applicants need to fully respect three eligibility criteria: 

  1. Early-stage researchers (ESR) are those who are, at the time of recruitment by the host, in the first four years (full-time equivalent) of their research careers. This is measured from the date when they obtained the degree which formally entitles them to embark on a doctorate, either in the country in which the degree was obtained or in the country in which the research training is provided, irrespective of whether or not a doctorate was envisaged.
  2. Conditions of international mobility of researchers: Researchers are required to undertake trans-national mobility (i.e., move from one country to another) when taking up the appointment. At the time of selection by the host organisation, researchers must not have resided or carried out their main activity (work, studies, etc.) in the country of their host organisation for more than 12 months in the 3 years immediately prior to their recruitment. Short stays, such as holidays, are not taken into account. 
  3. English language: Network fellows (ESRs) must demonstrate that their ability to understand and express themselves in both written and spoken English is sufficiently high for them to derive the full benefit from the network training.

The available 11 positions

ESR 1: Design, synthesis and optimization of inhibitors of enzymes involved in the sulfur assimilation pathway in Gram-negative bacteria
Objectives: Rational design and synthesis of a series of conformationally restricted small molecules inhibitors of O-acetylserine sulfhydrylase (OASS)-A, OASS-B, and serine acetyltransferase (SAT), enzymes involved in the last steps of sulfur assimilation pathway. Optimization of their PK properties.
Host: UNIPR Parma (Italy)
Supervisor: This email address is being protected from spambots. You need JavaScript enabled to view it.
Duration: 36 months
ESR 2: Characterization of S. typhimurium sulfur assimilation targets SAT and OASS
Objectives: To express, purify and characterize the enzymes SAT and OASS. To screen optimized OASS inhibitors and SAT ligands by activity assays and fluorimetric methods. To crystallize SAT and OASS in the absence and presence of inhibitors, and SAT-OASS complex. To identify the regulatory mechanisms controlling SAT, OASS and SAT-OASS activities. To investigate the expression of SRAP enzymes under different growth conditions via proteomic analysis of bacterial extracts.
Host: UNIPR Parma (Italy)
Supervisor: This email address is being protected from spambots. You need JavaScript enabled to view it.
Duration: 36 months
ESR 3: Systematic bioactivity evaluation of potential antibacterial agents in vitro: From biosensor-based HTS to follow-up studies
Job description: The main focus of the project is to develop advanced, cell-based and biochemical screening tools amenable for high-throughput screening and to demonstrate their functionality in antibacterial screening. You will evaluate the in vitro antibacterial properties of compounds provided by the consortium and validate the hits through a set of in vitro follow-up studies. In addition, you will be expected to write project reports, you will communicate with the other members of the consortium and will benefit from the training platform. 
Profile and requirements
  • You have a master degree, preferentially in pharmaceutical sciences, microbiology, biochemistry or molecular biology
  • You have a true research spirit and you enjoy problem solving
  • You are highly motivated to work in a multidisciplinary team
  • You have excellent organizational and communication skills and you are prepared to work under strict timelines
Host: University of Helsinki, Helsinki (UHEL, Finland), Centre for Drug Research, research group of Bioactivity Screening
Supervisor: This email address is being protected from spambots. You need JavaScript enabled to view it.
Duration: 36 months
ESR 4: Computer-aided drug design, hit finding and optimization
Objectives: To screen “in silico” new compounds against selected targets, analysis of in vitro results from (WP3) to select optimal hit compounds and to support medicinal and synthetic organic chemistry optimization of selected hit series together with WP2.
Host: UEF Kuopio (Finland)
Supervisor: This email address is being protected from spambots. You need JavaScript enabled to view it.
Duration: 36 months
ESR 5: Design and synthesis of mechanism based O-acetylserine sulfhydrylase inhibitors
Objectives: To develop mechanism based covalent inhibitors of OASS that can be used as tool compounds to investigate the role of OASS as antibacterial targets. These inhibitors serve as lead compounds for antibacterial drug discovery.
Host: LIOS Riga (Latvia)
Supervisor: This email address is being protected from spambots. You need JavaScript enabled to view it.
Duration: 36 months
ESR 6: The glyoxylate shunt as a target for antibacterial intervention in Gram-negative bacteria
Objectives: To characterize the enzymology controlling carbon flux through the TCA cycle / glyoxylate shunt branchpoint of the Gram-negative pathogen, Pseudomonas aeruginosa. To identify and characterize LMW compounds, which suppress carbon flux through the glyoxylate, shunt and thereby impair microbial fitness and virulence. To test these compounds for antimicrobial activity, determine their detailed MoA, and identify/characterize endogenous resistance mechanism(s), which reduce their potency.
Host: UCAM Cambridge (United Kingdom)
Supervisor: This email address is being protected from spambots. You need JavaScript enabled to view it.
Duration: 36 months
ESR 7: Discovery of novel gyrase B and gyrase B/topoisomerase IV (ParE) dual inhibitors with in vitro antibacterial activity
Objectives: Design, synthesis and evaluation of structurally novel gyrase B inhibitors and gyrase B/topoisomerase IV (ParE) dual inhibitors and achieving their in vitro antibacterial activity by modifications which will improve entry of inhibitors into bacteria.
Host: UL Ljubljana (Slovenia)
Supervisor: This email address is being protected from spambots. You need JavaScript enabled to view it.
Duration: 36 months
ESR 8: E. coli LsrK Kinase Inhibitors as Quorum Sensing interfering agents: validation of therapeutic potential
Objectives: Identify the first E. coli LsrK kinase inhibitors and evaluate their ability to impair bacterial growth based on QS interference. Assessment of whether QS inhibition is a feasible approach for antibacterial purposes.
Host: TAROS Dortmund (Germany)
Supervisor: This email address is being protected from spambots. You need JavaScript enabled to view it.
Duration: 36 months
ESR 9: Identification of novel covalent ClpP inhibitors as inhibitors of gram-negative bacteria
Objectives: This project focuses on identification and optimization of modulators (inhibitors and activators) of the bacterial ClpP enzyme using an interdisciplinary approach. By applying in silico and in vitro high-throughput screening techniques, the ESR will identify starting structures for novel antimicrobial agents. Compounds emerging as active from the screening step will be used in biochemical (target based) and cell-based (functional) assays to evaluate their antibacterial activity and to exclude compounds with off-target activities leading to unwanted side effects. In order to improve the antibacterial activity, most promising compounds will be chemically optimized by combining Computational and Synthetic Chemistry. During this project phase the scientist will be seconded to the University of Eastern Finland (Prof. Antti Poso) and the University of Antwerp (Prof. Koen Augustyns). Optimised compounds will be validated in successive rounds of experimental assays.
This project provides the unique opportunity for an ESR to receive an interdisciplinary training in early stage drug discovery, with an emphasis on antibacterial targets. The ESR will be directly involved in both experimental and in-silico based investigations. Within this combined inter-disciplinary approach the ESR will gain a broad exposure of both the needs of the pharmaceutical industry  and the increasingly important “open innovation” based academic approach to drug discovery.
Host: Fraunhofer IME, Hamburg (Germany)
Supervisors: This email address is being protected from spambots. You need JavaScript enabled to view it.  and This email address is being protected from spambots. You need JavaScript enabled to view it.
Duration: 36 months

ESR 10: Design, synthesis and characterization of novel modulators of ClpP proteases from Gram-negative bacteria
Job description: Building further on the experience of UAMC with enzyme inhibitors, you will focus on design, synthesis and characterization of novel modulators of ClpP, an emerging target in the antibacterial field.
  • You will be responsible for synthesis of the novel compounds
  • You will perform the analytical and biochemical evaluation of the compounds
  • You will write project reports for your supervisor on a regular basis
  • You will be working within our international group of 25 researchers
  • You will get in contact with the other members of this international consortium and will benefit from the training platform
  • Profile and requirements
  • You have a master degree, preferentially in chemistry or pharmaceutical sciences
  • You have a solid knowledge of synthetic organic chemistry and you are prepared to become an expert in medicinal chemistry
  • You have a true research spirit and you enjoy problem solving
  • You are highly motivated to work in a multidisciplinary team
  • You have excellent organizational and communication skills and you are prepared to work under strict timelines
Host: University of Antwerp (Belgium), research group of Medicinal Chemistry (UAMC), 
Supervisor: This email address is being protected from spambots. You need JavaScript enabled to view it.
Duration: 36 months
ESR 11: In vitro characterization and in vivo efficacy evaluation of selected compounds against relevant biofilm-producing Gram-positive and Gram-negative pathogens
Objectives: In vitro characterization of new chemical entities designed and selected during the project effort. Set up, validation and application of tailored animal models of bacterial infections for assessing the in vivo efficacy of selected compounds against biofilm producing bacteria and to develop PK/PD models for translation to clinic.
Host: APT Verona (Italy)
Supervisor: This email address is being protected from spambots. You need JavaScript enabled to view it.
Duration: 36 months

Public Abstract INTEGRATE

Antimicrobial resistance is posing a continuously-rising threat to global health. Indeed, one key recommendation from the recent “Action plan against the rising threats from Antimicrobial Resistance” report (submitted by the Commission to the European Parliament and Council (15.11.2011)) is the development of effective antimicrobials or alternatives for treatment of human and animal infections. The INTEGRATE project is a direct response to this. We have assembled a team of 10 beneficiaries from eight EU member states, encompassing both academic and non-academic sectors and different disciplines, to form a consortium committed to training Early Stage Researchers (ESRs) in the discovery and preclinical validation of novel Gram-negative antibacterial agents and antibacterial targets. The principle aim of the consortium is to provide a training platform where students are exposed to every aspect of the antimicrobial discovery process, ranging from target identification and validation, through organic synthesis, in silico design and compound screening, to mode-of-action and possible resistance mechanisms. This exposure will be accomplished through a concrete secondment plan, coupled with a series of high-level consortium-wide training events and networking programmes. Our intention is to reverse the current fragmentation of approaches towards antibacterial discovery through mutual cooperation. The INTEGRATE training framework is built on an innovative research project aimed at targeting important but non-essential gene products as an effective means of reducing bacterial fitness, thereby facilitating clearance of the pathogen by the host immune system. To achieve this, the individual work programmes have been designed to seamlessly inter-mesh contributions from the fields of in silico design, organic synthesis, molecular biology and biochemistry, and the very latest in vitro and in vivo screening technologies.

Beneficiaries: University of Parma, University of Helsinki, University of Eastern Finland, Latvian Institute of Organic Synthesis, University of Cambridge, University of Ljubljana, Taros Chemicals, University of Antwerp, Aptuit (Verona), and Fraunhofer
Partner Organisations: CSC - IT Centre for Science, Matera, Finnish Patent and Registration Office, and Tampere University of Technology

General contact persons:

Scientific Coordinator
Professor of Medicinal Chemistry, University of Parma, Dipartimento di Farmacia
Via Area delle Scienze, 27/a 43125 PARMA (Italy)

This email address is being protected from spambots. You need JavaScript enabled to view it.

Director of Training
Academy Research Fellow, Principal Investigator, University of Helsinki, Faculty of Pharmacy, Division of Pharmaceutical Biosciences, Centre for Drug Research
P.O. Box 56 (Viikinkaari 4), Room A326b, HELSINGIN YLIOPISTO (Finland)

This email address is being protected from spambots. You need JavaScript enabled to view it.

Project Manager
Research Manager, University of Helsinki, Faculty of Pharmacy, Centre for Drug Research
PL 56 (Viikinkaari 4), HELSINGIN YLIOPISTO (Finland)

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Appendix 1: Recruitment Procedure INTEGRATE – Full description

The Recruitment Committee (General Coordinator (GC) and one Supervisor per Beneficiary) oversees the recruitment of the 11 ESRs during the Recruitment event (5-6 May 2015, Verona). Initially, the search for the appropriate candidates is based on normal recruitment strategies (e.g., publication on ec.europa.eu/euraxess, etc.; personal contacts of the network partners). The pre and final selection will be made in a collective process, led by the Recruitment Committee (RC), which consists of experts highly experienced with selection procedures. The candidates apply for maximum three specific projects and list their order of preference. Applications are made on-line through the appropriate website. Approximately 30 fellows are invited to the Recruitment Workshop (Verona, 5-6 May 2015). In order to facilitate their travel, selected candidates (if outside Italy) will receive a fixed, lump sum of 250 euro. Each candidate gives a presentation and is interviewed. The committee selects the ESRs (1) based on their scientific background and potential, (2) based on the expected benefit of scientific exchange between the trainees’ home countries and institutions and the hosts, and (3) in accordance to gender equality and minority rights. The candidates are ranked and a collective decision is made, taking into account the order of preference. The envisioned Supervisor gets the final say. In this way a complementary team of ESRs can be assembled. All recruitment is in line with the European Charter for Researchers, providing the overarching framework for the roles, responsibilities of both researchers and employers. The Code of Conduct for the Recruitment of Researchers functions as a set of principles and ensures that the selection procedures are transparent and fair. The recruitment strategy of INTEGRATE fully complies with the Code of Conduct definition of merit. For example, merit is not only measured on researcher’s grades, but on a range of evaluation criteria, such as teamwork, interdisciplinary knowledge, soft skills and awareness of the policy impact of science. The RC has members of each gender and considers the promotion of equal opportunities and gender balance as part of the recruitment strategy. Special efforts are made to attract women and fellows from new EU member states. INTEGRATE aims at a participation of 50% women in the network. Among equally qualified applicants, women receive preferential consideration. Researchers are employed on fixed term contracts and are registered as staff candidates for PhD degrees. Therefore, they are entitled to pension contributions, paid holidays, and other employment benefits as governed by the universities and industrial companies. In case not all ESRs can be recruited during the collective Recruitment Event, the recruitment procedure is “decentralised”, meaning that the Involved Supervisors will continue the search for good candidates and have the authority to decide which person they recruit. However, the GC will be kept informed at all times when new eligible candidates appear. The GC will make an official complaint in case the Code of Conduct for the Recruitment of Researchers is breached. The Involved Supervisor is then expected to find another candidate. Recruitment problems will also, if still needed, be discussed during the Recruitment Committee meeting (Month 6) in order to deliver specific action plans to target specific networks relevant for any missing ESR positions. Recruitment committee: Gabriele Costantino, Andrea Mozzarelli (UNIPR), Päivi Tammela, (UHEL), Antti Poso (UEF), Aigars Jirgensons (LIOS), Martin Welch (UCAM), Danijel Kikelj (UL), Fabrizio Giordanetto (TAROS), Philip Gribbon (ESP), Koen Augustyns (UA), Antonio Felici (APT). Paul Bromann (UHEL) will facilitate the whole procedure.