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Jobs

14 PhD positions in the EU Horizon 2020 Marie Skłodowska-Curie Project PRECODE:

International training network which sets a joint research programme to train a new generation of leading scientists in model systems and methods for the development of new therapies for pancreatic cancer (PaCa)

The main PRECODE R&D objectives are:

  1. To establish an European resource of pancreatic cancer organoid and integratomic analysis of those organoids.
  2. Identify drug resistance and sensitivity in those organoids to develop new treatment and diagnostic strategies.
  3. To improve organoid culture and establish a model system containing all parts of a pancreatic cancer tissue for growing in vitro.
  4. To identify new genes essential for pancreatic cancer progression and metastasis.

Career stage

Early Stage Researcher (ESR) or 0-4 yrs (Post Graduate)

Benefits

The successful candidates will receive an attractive salary in accordance with the MSCA regulations for Early Stage Researchers. The exact (net) salary will be confirmed upon appointment and is dependent on local tax regulations and on the country correction factor (to allow for the difference in cost of living in different EU Member States). The salary includes a living allowance, a mobility allowance and a family allowance (if married). The guaranteed PhD funding is for 36 months (i.e. EC funding, additional funding is possible, depending on the local Supervisor, and in accordance with the regular PhD time in the country of origin). 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.

Eligibility criteria

Applicants need to fully respect three eligibility criteria (to be demonstrated in the Europass CV format):

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.

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.

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.

Selection process

Deadline for applications is 2.12.2019. To attract the right students, the required profiles are clearly listed for each ESR position.

The candidates apply for a maximum of three specific ESR positions and list their order of preference. The Supervisors provide the names of their preferred candidates to the Supervisory Bord (SB), which in its turn produces a short list. After a thorough evaluation, the candidates are ranked and a collective decision is made. In this way a complementary team of ESRs can be assembled, as positively experienced from previous ETN recruitment events.

The SB is kept informed at all times when new eligible candidates appear. The SB makes 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.

All chosen candidates are expected to start their contract by the end of February 2020.

All details concerning the recruitment-procedure principles are communicated on the on-line application portal, so that potential ESRs know exactly what to expect and are stimulated to apply. All recruitment (pre and final selection) 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 ensures that the selection procedures are transparent and fair.

Additional comments

The recruitment strategy of PRECODE fully complies with the Code of Conduct definition of merit. For example, merit is not just measured by a 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 SB has members of each gender and considers the promotion of equal opportunities and gender balance as part of the recruitment strategy. Also, in view of the RRI principles, special efforts are made to attract women and ESRs from new EU Member States.

PRECODE aims at a participation of 50% female ESRs in the network. 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 benefits as governed by the universities and industrial companies.

14 PhD positions in the EU Horizon 2020 Marie Skłodowska-Curie Project PRECODE

Host: Universitätsklinikum Erlangen

Main supervisor: Prof. Christian Pilarsky (Christian.pilarsky@uk-erlangen.de)

Duration: 36 months

Required profile: Master in Life Sciences, Experience in Molecular Biology

Description: Organoids are a new model system in cancer research and they enable researchers to identify new genetic components in pancreatic cancer progression and metastasis in an unprecedented manner. Organoids can be isolated from various diseased tissues and manipulated by different techniques. The successful applicant will learn to isolate and cultivate organoids from different sources. He or she will establish organoids which contain the libraries of sgRNAs. He or she will then screen these GEPOs for resistance against different drugs and for changes in the migratory/invasive pattern. The candidate will identify and validate sgRNAs which confer resistance and changes in migratory patterns.

Host: Friedrich-Alexander University of Erlangen-Nürnberg

Main supervisor: PD Dr. Marc Stemmler (marc.stemmler@fau.de)

Duration: 36 months

Required profile: Master in Life Sciences, Experience in Molecular Biology

Description: The lab is focused on understanding molecular mechanisms of metastasis formation and we have collected ample evidence that Zeb1-depletion diminishes cell plasticity required for efficient metastasis in a genetic mouse model of pancreatic cancer. Using pancreatic cancer organoid cultures, genetic engineering and screening methods we want to decipher the molecular mechanisms how Zeb1 regulates cell plasticity and metastasis. The applicant will learn how to use specific autochthonous mouse models for isolation, culturing and in vitro manipulation of Zeb1 proficient and deficient organoids. The successful candidate will set-up screening methods to identify candidates mediating drug sensitivity, cell plasticity, motility and metastasis. By CRISPR/Cas9 technology candidate genes will be knocked out and phenotypical changes assessed by analysis in gene expression pattern, migration/invasion potential and transplantation experiments.

Host: Mimetas BV, The Netherlands

Main Supervisor: Dr Karla Queiroz, (k.queiroz@mimetas.com)

Duration: 48 months

Required profile: The applicants should preferably hold an MSc degree in Biological Sciences or a related discipline. Interest in developing and translating technology to establish new tools for biomedical research is a plus. Strong understanding in Cell and Molecular Biology. Good knowledge of (3D) cell culture and laboratory equipment such as microscopes and plate readers is desirable. Knowledge in the field of organ-on-a-chip and pancreatic cancer are great assets

Description: MIMETAS develops and validates customised disease-, toxicology- and transport tissue models using organ-on-a-chip technology for drug screening in 3D-tissues. Our unique microfluidic platform enables testing of compounds in high-throughput on miniaturized organ models. These models may offer better predictivity as compared to laboratory animal testing and conventional cell culture models. The MIMETAS OrganoPlate® platform supports 3D cell culture under continuous perfusion, membrane-free co-culture and boundary- and gradient formation. It thus can mimick important aspects of tissues and organs. MIMETAS has an open culture, where achievements go hand in hand with a fun place to work. Our close-knit team stays successful by maintaining a good atmosphere while working in a highly competitive field. MIMETAS’ headquarters are based in Leiden, The Netherlands and our manufacturing facility is based in Enschede, The Netherlands.  We have subsidiaries in Gaithersburg, MD, USA and Tokyo, Japan. The successful PhD candidate will work at Mimetas and develop translational pancreatic cancer patient-derived models using the OrganoPlate platform. PhD candidate will be part of the Model Development team  (led by Dr Henriëtte Lanz) and supervised by Dr Karla Queiroz.

Host: Karolinska Institutet

As a university, KI is Sweden’s single largest centre of medical academic research and offers the country’s widest range of medical courses and programmes. Since 1901 the Nobel Assembly at Karolinska Institutet has selected the Nobel laureates in Physiology or Medicine. Karolinska Institutet was founded by King Karl XIII in 1810 as an “academy for the training of skilled army surgeons”. Today, Karolinska Institutet is a modern medical university and one of the foremost in the world. With the close relationship to the clinical milieu, a well established infrastructure and a stable financial situation, Karolinska Institutet has excellent prerequisites for sustaining high quality research and education.

Main supervisor: Prof. Matthias Löhr (Matthias.lohr@ki.se)

Duration: 36 months

Required profile: Master in Life Sciences, Experience in Molecular Biology

Description: Culture of cells in 3D is much closer to in vivo growth than 2D culture of cells for many reasons. In recent years it has been demonstrated that growth and therapeutic response behaviour of cancer cells is greatly dependent of their microenvironment. We grow pancreatic cancer cells (monospheroid) alone or together with pancreatic stellate cells (heterospheroid) in 3D in order to learn more about their mutual dependencies and vulnerabilities. In addition, we use these models for high throughput drug screening. The future student will learn 3D culture methods using cell lines as well as patient material and he/she will analyse these cultures by RNAseq in order to identify points for therapeutical attack. This will be complemented by high throughput/content drug screening approaches.

Host: University of Verona

Main supervisor: Dr Vincenzo Corbo (Vincenzo.corbo@univr.it)

Duration: 36 months

Required profile: Master in Life Sciences, Experience in Cell and Molecular Biology, experience of computational biology is a plus

Description: Patient-Derived Organoids (PDOs) are a new biological platform to understand the biology of pancreatic cancer. PDOs can be successfully derived from majority of pancreatic cancer patients and also enable the cocultivation of neoplastic cells with other cellular components, including cancer-associated fibroblasts (CAFs). The successful applicant will learn how to isolate, cultivate and characterize both PDOs and (CAFs). He or She will establish PDOs representative of the different molecular subtypes of pancreatic cancer and study their interaction with CAFs. He/She will subject both PDOs and coculture of PDOs and CAFs to pharmacological treatment to establish resistance/sensitivity of the culture. To understand mechanisms of resistance to a given compound, and specifically the contribution of cell plasticity to this phenomenon, the candidate will avail of single cell sequencing analysis organoids.

Host: Academic Medical Center

Main supervisor: Dr. Maarten Bijlsma (m.f.bijlsma@amsterdamumc.nl)

Duration: 48 months

Required profile: master’s degree in life sciences, other (bio)medical sciences or related. Basic bioinformatics and cell culturing skills. Applicants can have any nationality, but the MSCA-ITN mobility clause applies (more than 24 months of the past 3 years were spent outside of the Netherlands).

Description: Of all common solid cancers, pancreatic cancer has the worst prognosis. Despite intense research efforts, the prognosis of this disease has only minimally improved over the last decades and it is clear that novel research approaches are required. The recently established PRECODE European consortium aims to leverage organoids as a novel experimental model system to better understand key processes that underlie pancreatic cancer progression and metastasis. In pancreatic cancer, the collective of non-tumor cells in a cancer called stroma, is suspected to contribute to poor outcome by driving aggressive tumour cell behaviour. In this project, the applicant will identify and target candidate genes suspected to mediate tumour-stroma crosstalk and assess their potential as biomarkers in the context of organoid (co)cultures. The applicant will contribute to the generation of organoids for the consortium by accruing patients and culturing biopsy material at the Amsterdam UMC (location AMC, CEMM/LEXOR department), and in collaboration with the other PhD candidates in the consortium, establish the optimal culturing conditions that allow meaningful drug screening and other experimental manipulations. Several gene expression-based classification methods have been described that identify subgroups of pancreatic cancer. These also relate to tumor-stroma crosstalk and bear relevance for treatment outcome. To enable meaningful and uniform classification of the pancreatic cancer organoids to be used in the consortium, the applicant will develop a classification method to accurately assign organoids to molecular subgroups and assess the stromal contributions to these. The overarching aim of this basic and translational research is to improve the outcome of a devastating disease.

Host: Umeå University

Main supervisor: Assistant Professor Daniel Öhlund (daniel.ohlund@umu.se)

Duration: 48 months

Required profile: Medical degree, Master in Life Sciences, Experience in Molecular Biology

Description: The ESR will work in the network to refine the isolation and culturing conditions for human pancreatic and stroma cell co-cultures, and participate in the development of assays for high-throughput screenings of human co-cultures. By manipulating the expression of the extracellular matrix (ECM) proteins in the co-culture model and assay the biological changes in the co-culture, the goal is to get a deeper understanding in the functional diversity found in the ECM of pancreatic cancer. This will help us to define stromal elements that contribute differently to the pathophysiology of pancreatic cancer. This knowledge will then be used to develop and test drugs that selectively target the pro-tumourigenic interactions between the tumour cells and the ECM.

Host: University of Navarre in Pamplona, Spain (Clinica Universidad de Navarra and Center for Applied Medical Research -CIMA-)

Main supervisor:  Dr. Mariano Ponz-Sarvise (e-mail: mponz@unav.es)

Duration: 36 months

Required profile: The applicants should preferably hold an MSc degree in Biological Sciences or a related discipline

Description: The successful PhD candidate will work in the laboratory of Oncogenes and Effector Targets (OnTarget) under the guidance of Dr. Ponz-Sarvise. The group is part of the Solid Tumors Program and is located at the Center for Applied Medical Research, CIMA, in the campus of the University of Navarre. The OnTarget group focuses on KRAS-driven tumors and studies are based on a multimodal approach, which includes functional genomic techniques, mouse genetics, in vitro and xenograft models, analysis of human cancer samples, and clinical parameters. The laboratory also works with organoids from primary human and murine cells. This model makes it possible to carry out in vitro and in vivo studies of gene modulation, pharmacological treatments and cell co-cultures. The overarching goal of the group is to identify molecular targets and/or combinatorial therapeutic approaches that will provide effective treatments for patients harbouring KRAS mutations. The main research lines of the OnTarget group are: 1) to unveil key nodes of gene expression regulation (transcription factors and miRNAs) and tissue-dependent KRAS synthetic lethal interactions that will yield new molecular targets, and 2) to dissect the efficacy of targeted therapy- and immunotherapy-based strategies for the treatment of mutant KRAS cancers. In the last years the group has developed new computational analyses and mouse models that provide the methodological ground for ongoing work. This methodology has provided the seed results to engage international (Systems Biology Ireland, BRIC of Copenhaguen, UCSF, Stanford University) and national (CNIO, VHIO, Biodonostia) groups in active collaborations.

The successful ESR will develop a PhD project focused on an organoid co-culture platform for the development of rational combinations in the field of immune-oncology. The objectives of the project would be: 1) Development of a platform for co-cultivation of pancreatic organoids with cancer-associated fibroblasts and immune cells obtained from patients affected of pancreatic cancer. 2) Drug effects in the different cell types that form the tumour (including stroma). 3) Identification of rational combinations and preclinical studies to test the effect of the combinations. The co-culture platform will be used to analyse both at the cellular and molecular level the effect of the drugs in the different cell types that form the tumour (including the stroma). This analysis will enable to define combination strategies of cytotoxic drugs or targeted therapies with immune-modulatory drugs.

The project should be developed in 3 years. During this period the successful ERS will perform two additional training sessions (secondments) of three months each in:

  • UNIVERSITA DEGLI STUDI DI VERONA, Italy, under the supervision of: Vincenzo Corbo to learn to establish and expand organoid cultures

MIMETAS BV, Netherlands, under the supervision of Remko van Vught about the development and optimisation of assay techniques for co-cultures

Host: Institute of Cancer Sciences (ICS), University of Glasgow, United Kingdom

Main Supervisor: Dr Peter Bailey (peter.bailey.2@glasgow.ac.uk)

Duration: 36 months

Required Profile: Master’s degree in Bioinformatics, Life Sciences, Biomedical Science or related discipline. Although not essential bioinformatic experience is preferable. Applicants can have any nationality, but the MSCA-ITN mobility clause applies (more than 24 months of the past 3 years were spent outside of the United Kingdom).

Description: Large scale sequencing analyses have transformed our understanding of Pancreatic Cancer (PC) and have defined several molecular taxonomies that now guide pre-clinical and clinical therapeutic development. The identification of molecularly defined subgroups of patients with distinct biological underpinnings and potential therapeutic vulnerabilities promises a step change in clinical practice. Patient-derived organoids (PDOs) provide a tractable and biologically relevant model system for understanding the molecular mechanisms underpinning disease progression and drug resistance. The PRECODE consortium aims to perform a deep characterisation of ~200 PDOs using cutting edge techniques to uncover new biology and provide a basis for clinical decision making.

The successful PhD applicant will play a central role in the molecular characterisation of ~200 PDOs using RNAseq and Whole Exome Sequencing (WES). The applicant will implement best practice pipelines for NGS analysis and develop systems biology approaches to identify therapeutically actionable pathways for clinical development. The applicant will work closely with other groups within the consortium to facilitate the deep interrogation of high throughput drug and metabolomic screening data and to develop signatures of drug response and resistance. It is expected that the applicant will develop core competencies in bioinformatics including software development (working knowledge or R and python), database development and management, data visualisation, statistical analysis and systems biology approaches for data analysis.

Host: CELLPHENOMICS GmbH

Main supervisor:  Dr. Christian Regenbrecht (christian.regenbrecht@cellphenomics.com)

Duration: 36 months

Required profile: Medical degree, Master in Life Sciences, Experience in Molecular Biology

Description: The successful candidate will develop new and integrated platforms for high throughput screening. He or she will identify new compounds for identified mutations in drug screen.
Using the existing drug screening platform of cpo the successful candidate should develop new methods and protocols for high throughput screening of pancreatic cancer organoids and validate vulnerabilities identified by WP2 and modelled by WP6. To integrate existing platforms the successful candidate will analyse the different possible substrates available developed by WP1.

Host: Leiden University

Main supervisor: Prof. Thomas Hankemeier (hankemeier@lacdr.leidenuniv.nl)

Duration: 48 months

Required profile: Medical degree, Master in Life Sciences, Experience in Molecular Biology

Description: The work is highly interdisciplinary and the successful candidate is embedded in a team with engineering and analytical, biochemical, clinical and biomarker experts, biostatisticians, and IP managers. The successful candidate is going to learn and develop highly innovative miniaturized metabolomics technology and methods and data analysis of multi omics data to find, interpret and develop biomarkers using metabolomics/transcriptomics. Objectives are: (1) Establish a miniaturized metabolomics method for organoids. (2) Characterise the metabolome of pancreas organoids in respect of or response to cultivation, genetic pattern, malignancy, treatment and resistance. Metabolomics data will include a. o. central carbon/energy and lipid metabolism, signalling lipids and mediators, oxidative stress. (3) Integrate metabolomics and transcriptomics data and evaluate potential of co-regulated biomolecules as drug target candidates or prediction markers in terms of stratified/precision medicine. (4) Identify suitable biomarkers for mode of action elucidation of active compounds.

Host: AstraZeneca

Main supervisor: Dr. Simon Barry (Simon.T.Barry@astrazeneca.com)

Duration: 36 months

Required profile: Medical degree, Master in Life Sciences, Experience in Molecular Biology

Description: Imuno-oncologic perturbation with checkpoint inhibitors is a recent field of cancer treatment. Within this project we will identify factors which will improve the treatment outcome if checkpoint-inhibitors in PaCa. Therefore we will treat co-culture of PaCa organoids with different substances modulating the growth of organoids and/or modulating the response of lymphocytes to PaCa. The successful candidate will analyse different small drug checkpoint inhibitor combinations to evaluate responses in organoid growth.

Host: The Medical University of Gdańsk

Main supervisor: prof. Iwona Inkielewicz-Stępniak (iwona.inkielewicz-stepniak@gumed.edu.pl)

Duration: 36 months

Required profile: Master in Medical, Life or Biological Sciences, experience in cell culture, western blot technique, flow cytometry. Experience in platelet isolation is very welcome.

Description: Organoids are a new model system in cancer research and they enable researchers to perform screening of new potential drugs taking into account penetration and interaction with the extracellular matrix components (ECM). Platelets play a key role in metastasis of cancer cells and their interaction with tumour microenvironment, including ECM, can provide an important therapeutic target. The ESR will learn to isolate and cultivate pancreatic organoids from different sources as well as platelet from blood samples. The ESR will develop a new model for study the interaction between organoids and blood platelets collected from patients with pancreatic cancer cells to measure tumor cells-induced platelets aggregation (TCIPA): aggregation, cell viability and secretion of growth factors. We will attempt to use our model to check influence of blood platelets on chemoresistance, metastasis as well as to assess the impact of new synthesized nanoparticles-drugs on pancreatic cancer cells death (apoptosis, necroptosis) using organoids.

Host: Trinity College Dublin, Ireland

Main supervisors: Prof. Maeve Lowery (mlowery@tcd.ie). Dr Naomi Walsh

Duration: 36 months

Required profile: BSc  / MSc in Biological Sciences or related discipline

Description: The successful PhD candidate will work at the Trinity Translational Medicine Institute, Trinity College Dublin and The National institute for Cellular Biotechnology, Dublin City University in Dublin, Ireland in the groups of Prof Maeve Lowery and Dr Naomi Walsh.  The labs utilise genomic and functional NGS approaches to identify the mechanisms of genomic diversity to develop prognostic/predictive signatures and therapeutic strategies to overcome treatment resistance in cancer.

The successful ESR will perform functional analysis of DNA repair proficiency in pancreatic organoids including proficiency of homologous recombination repair, replication fork protection and analyse the somatic and germline genome for alterations in genes associated with repair pathways using WES / panel based sequencing. The project goals are to develop an in vitro assay for predicting response to DNA damaging agents in the clinic and identify novel mechanisms of drug resistance.