The candidate will be jointly supervised by Prof Pier Giuseppe Pelicci and Dr Luca Mazzarella to explore molecular mechanisms of acute myeloid leukemias (AML).
The lab is extensively exploring the interaction between systemic metabolism (modulated by obesity, caloric restriction, intermittent fasting), chromatin dynamics and the regulation of protein quality control (ER stress, UPR) in mouse models of AML, a research project stemming from clinical observations (Breccia, Mazzarella et al Blood 2012).
In particular, we have intensively investigated the biology of the FLT3 kinase, the most commonly mutated gene in AML. We have found that the most frequent genetic alterations involving FLT3 perturb the phyisological folding, maturation and intracellular localization of the protein. This causes global alterations in cellular metabolism which may be favoured by specific dietary components, and creates vulnerabilities that could be targeted pharmacologically.
The candidate will be asked to pursue a research program aimed at exploring the biology of mutant FLT3 using a combination of imaging, transcriptomics, proteomics and metabolomics techniques.
The candidate will join a growing and stimulating research environment at the interface between the clinics and the lab, in a research institute of excellence with state-of-the-art equipment for:
- DNA/RNA sequencing (Illumina Novaseq and Hiseq, Chromium 10x, Nanopore MinIon and GridIon sequencers). In particular the institute has accumulated wide experience on single-cell sequencing (largest center in Italy by volume).
- imaging, with multiple confocal microscopies (Leica DM6-B, SP8-CSU, SP8-FSU, TIRF) and equipment for live cell-imaging.
- flow cytometry with 3 analyzers (2 FacsCelesta, 1 MACSQuant) and 3 cell sorters (FACSMelody, FacsAria Fusion and FacsJazz).
- proteomics/metabolomics unit equipped with a Q Exactive HF hybrid quadrupole-Orbitrap mass spectrometer coupled with a EASY-nLC 1200 Ultra-HPLC chromatography.
- PhD-level background in biology, medicine or biotechnology.
- Documented experience with in vivo mouse models for molecular oncology (specific experience in hematology is highly desirable).
- Familiarity with flow cytometry and fluorescence microscopy.
- Documented experience in at least one of the following: RNAseq, signal transduction analysis, metabolomics, proteomics, endoplasmic reticulum biology.
- Ability to work independently and as part of a team.
- Very good oral/written communication and interpersonal skills.
- Ability to independently write research reports and publications for peer reviewed journals.