The Machine Materials Laboratory at the institute of Physics of the University of Amsterdam is looking for excellent, highly motivated postdoctoral research c…
PhD student KwF Project PMC
- Lundlaan, Utrecht, Utrecht
- Tijdelijk contract / Tijdelijke opdracht
- Uren per week:
- 36 uur
- € 2567 - € 2960 per maand
Over the last decade, intensive multi-agent combination treatment has boosted survival and cure to approximately 80 percent of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients. The outcome for relapsed patients remains poor, and ...
Over the last decade, intensive multi-agent combination treatment has boosted survival and cure to approximately 80 percent of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients. The outcome for relapsed patients remains poor, and acquired therapy resistance characterizes relapsed T-ALL in particular. A major disadvantage of high-intensive treatment protocols is the frequent appearance of detrimental late toxic effects. Therefore, new cancer therapies by the introduction of high precision medicines is urgently needed in clinical practice as part of patient-tailored treatment that prevents disease relapse and improves cure-rates while diminishing late treatment effects.
In this current PhD-project, we will use next-generation sequencing and phospho-proteome profiling to identify mutations in signaling molecules or aberrantly activated pathways in pediatric T-cell acute lymphoblastic leukemia to pinpoint chromosomal rearrangements, mutations or aberrantly (in)activated molecules that represent important regulators of leukemia maintenance and growth. These data will be related to leukemia response levels to clinically relevant precision inhibitors as tested in high throughput cytotoxicity assays, and will form the rational for targeted treatment by small molecule, precision medicines in future treatment strategies. Promising inhibitors will be tested as proof-of-principle for their therapeutic potential to eradicate T-cell leukemia cells in xenotransplantation models of patient-derived leukemic cells. Results as obtained in this project may pinpoint activated or mutant molecules that can serve as molecular biomarkers to predict sensitivity of T-ALL patients to specific new precision inhibitors and provide a rational for future clinical trials for T-ALL patients.
Tasks and responsibilities
- The PhD-student will be responsible for preparation of primary patient samples for whole-genome sequencing, (phospho-)proteomic profiling and cytotoxicity screening, and work in close collaboration with postdocs, PhD-student and bioinformaticians within the T-ALL research group in the PMC as well as working at the OncoProteomics Lab at the VUmc in Amsterdam. The PhD-student will remain up to date with respect to new developments in the field.
Specific tasks will include
- Collection and preparation of primary patient materials for WGS and (phospho-) proteomic profiling.
- Will perform (phospho-)proteomic experiments at the VUmc
- Will conduct cytotoxicity screens in-vitro based on primary patient materials.
- Will closely collaborate with bioinformaticians, postdocs and technicians in both labs for analyzing WGS and proteomic datasets in relation to cytotoxic response levels to targeted inhibitors.
- Perform in-vivo validation experiment using xenograft transplantation models for effective targeted compounds.
Education and skills
- Background in molecular biology/biochemistry, experience with proteomics is an advantage
- Affinity with working with large molecular profiling datasets, expertise with the statistical environment R is an advantage
- Willing to work with patient models based on xenograft transplantations
- Strong drive for career in science with an inquisitive, creative mind
- Strong communicative skills (oral and written)
- Self-critical mindset and can-do mentality
- Independent working style but candidate will also closely collaborate with bioinformaticians and scientists in an (interdisciplinary) setting.
- Flexibility in working in two locations, as the work requires
- The Princess Máxima Center operates according to the ‘CAO algemene ziekenhuizen’
- Your salary is being fixed as follows on the basis of PhD-student scale equivalents in the collective labour agreement excluding 8% holiday allowance and an 8,33% year-end bonus. The gross salary will be 2.567 euro per month in the first year (2.960 gross in the fourth year).
Remarks and contact
We offer a PhD-position for 4 years, starting with an one year contract. Additional information about the vacancy can be obtained from Dr. J. Meijerink (email@example.com). Detailed information about the Princess Máxima Center for Pediatric Oncology can also be found at www.prinsesmaximacentrum.com and of the OncoProteomics Laboratory of the VUmc at www.oncoproteomics.nl . Applicants can send a letter of intent outlining special interest in the position, overall related qualifications, experience and career goals, a curriculum vitae and names and addresses of professional references.
The Princess Máxima Center for Pediatric Oncology is a recently started, fast growing national research hospital for the treatment of children with cancer. The institute houses an increasing number of research groups, which aim to develop curative treatment strategies for all children with cancer and minimizing long-term detrimental side effects of treatment.Childhood T-cell malignancies Research Group
The group of Childhood T-cell malignancies Research Group aims to develop new targeted therapeutic strategies that are directed against cancer-driving processes. Our research is focused on:
- the identification of (combinations of) disease-driving genetic aberrations at disease diagnosis and relapse.
- genetic aberrations that are associated with therapy resistance.
- development of targeted therapeutic approaches that are directed against cancer-driving lesions or leukemia mechanisms of therapy resistance.
The OncoProteomics Laboratory (head Prof. Connie Jimenez) focuses on the application of innovative mass spectrometry-based (phospho)proteomics and data analysis to improve diagnostics and treatment of cancer.
Within this research collaboration, in the context of a joint KWF project entitled “Identification of biomarkers by whole-genome sequencing and phospho-proteomics to predict responses to high-precision cancer medicines in T-cell acute lymphoblastic leukemia”, we currently have a vacancy for molecular biological-trained PhD-student (AIO) with affinity for OMIC research and data mining.
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