Metastatic melanoma is a hard-to-treat disease and it remains as one of the most worrisome cancer. There is an urgent need to improve the current therapies (chemotherapy, radiotherapy) that have a limited efficacy. A single therapy is not efficient to tackle metastatic melanoma and a combination of therapies is thus emerging as a necessity to efficiently eradicate all cancer cells. Recently, the chimeric antigen receptor (CAR)-T cell immunotherapies have shown outstanding results in hematologic malignancies. Nevertheless, the physical barriers represented by cellular and non-cellular components of the tumor microenvironment combined to the abnormal vasculature and high interstitial fluid pressure, hamper an efficient tumor infiltration of CAR-T cells in solid tumors. In this context, thanks to a network of 18 partners (including 10 non-academic partners), MELOMANES aims to train 12 doctoral researchers for the development of a combined therapy exploiting the properties of magnetic nanoparticles to disrupt these barriers, i.e. the tumor microenvironment, by magnetic and optic hyperthermia in order to facilitate the infiltration of CAR-T cells. Research and transferable training of the doctoral researchers will be performed in a highly interdisciplinary, intersectoral, and international environment. In addition to acquiring skills related to the research project, they will be trained also in open science, communication and dissemination, responsible research and innovation, circular economy, ethics, data management, entrepreneurship, marketing, intellectual property, and gender dimension in research. Their competences will be validated through certification and qualification examination, allowing a new generation of highly skilled doctoral researchers to emerge with a high-level training in particular in the multidisciplinary field of nanomedicine.
The purpose of this PhD project is to perform in vitro and ex vivo OMICS-based high-throughput assessment of toxicity and cellular interactions of engineered magnetic nanoparticles (NPs) to support rapid development and clinical uptake. This PhD project will utilize integrated novel methodologies, including 1. Advanced cell-based ex vivo and in vitro high-throughput screening using patient-derived primary tumor cell cultures and established cell lines for therapeutic potentiation of the uptake and efficacy of the NPs, 2. Toxicogenomics for modelling adverse outcome pathways and safety assessment; and 3. In silico analyses to identify biological interactions of the NPs. The research will focus on cell-based toxicity and therapy efficacy assessment, and, significantly, on producing large volume of biological multiomics data on cellular processes affected by the iron carbide NPs using the Tox5 score developed by Misvik Biology. In addition, state-of-the-art organ-on-chip technologies and other new approach methodologies developed by the Melomanes partners will be used to validate findings to develop the best models into potential biomarkers and therapeutic strategies for the iron carbide conjugates for cancer therapy.
- Apply multiomics data derived with ex vivo tissue and cell models for the analysis of the safety of the magnetic nanoparticles.
- Assess and predict the toxicity and biological activity of the magnetic NPs.
- Identify combinatorial therapeutic strategies to potentiate the uptake and efficacy of the NPs.
- Identification and characterization of cellular processes affected by the exposure of human cells and tissues to the multifunctional NPs.
- Categorization of the nanotoxicology profiles of the new materials to existing nanosafety records of nanomedicines.
- Identification of targets to be used for sensitising cancer cells with the multifunctional NPs.
Supervisors and host organisations
Dr. Juha K. Rantala, Misvik Biology Oy, Turku, Finland,
Dr. Vesa Hongisto, Misvik Biology Oy, Turku, Finland,
Co-supervisor (academic partner):
Prof. Davide Bonifazi (University of Vienna)
Dr. Emmanuel Donnadieu (National Institute of Health & Medical Research, INSERM)
Planned mobility track and secondments:
INSERM; France (6 months, M16-M21): Assessment of the safety of multifunctional iron carbide NPs using tumor slices.
University of Vienna; Austria, (4 months, M30-M33): Biodegradation of the NPs monitored by physicochemical characterization
Enrolment in Doctoral School:
University of Turku, Drug Research Doctoral Programme (DRDP), Turku, Finland
We are looking for an excellent candidate interested in combining cell-based multiomics data with advanced bioinformatics analyses to advance the use and efficacy of the novel nanomaterials as new approaches for more effective cancer therapies. The successful candidate should hold a MSc degree in relevant biological sciences, bioinformatics or a related discipline and preferably have previous experience in next generation RNA/DNA sequencing analyses.
The successful candidate should preferably have previous experience in multiomics data and bioinformatics.
The candidate, at the time of recruitment, must hold a Master’s degree.
The candidate must not have resided or carried out their main activity (work, studies, etc.) in Finland for more than 12 months in the 3 years immediately before the recruitment date. Compulsory national service, short stays such as holidays, and time spent as part of a procedure for obtaining refugee status under the Geneva Convention are not considered.
The candidate, at the time of recruitment by Misvik Biology must not be enrolled in a doctoral school or have been awarded a doctoral degree.
WHAT WE OFFER
- An enrolment in an industrial PhD program: https://www.utu.fi/en/research/utugs/drugresearch-doctoral-programme ;
- An international work environment, in which doctoral researchers can develop their skills and innovate within a competent team;
- An attractive 36 months’ salary;
- An individual and well-structured scientific and transferable training (open science, responsible research and innovation, circular economy, ethics, data management, entrepreneurship, creativity, communication, career plans and gender balance in science) within the Melomanes network.
- Motivation letter (max. 2 pages);
- CV including the details of education/qualifications, work experience, language skills and other relevant skills; indication of at least two Scientists for reference letters (academic and/or nonacademic);
- Certified/signed copy of a recent transcript of exams taken with relative mark. A certified/signed copy of Master of Science certificate or a letter from the Head of the degree course stating that the Student is going to finish before the September 2023;
- A summary of your research projects (max. 5 pages).
All applications will be checked for eligibility (in particular, the adherence to the mobility rule). Incomplete applications will be ignored. Shortlisted candidates will be invited for an interview. Candidates will be notified of the outcome. Start of employment is foreseen February 2023.
You should send your application to: [Email Address Removed]