PhD position (m/w/d) Department of Medicine V, Hematology, Oncology, Rheumatology

The University Hospital Heidelberg is one of the major healthcare centers in Germany. Our objective is the development of innovative diagnostics and therapies as well as their quick implementation for the patient. With about 14,000 employees in more than 50 specialized clinical departments with almost 2,500 beds, about 80,000 patients in part-time and full-time inpatient treatment as well as 1,000,000 patients in ambulant treatment are medicated each year. PhD position (m/f/d) Multimodal approaches to understand and overcome niche-related adaptive drug resistance in FLT3-mutated AML wanted for the next possible date at the Department of Medicine V, Hematology, Oncology, Rheumatology

For our project “Multi-modal proteomics to understand and overcome niche-related adaptive drug-resistance mechanisms in FLT3-mutated AML” we are looking for a PhD student. The project is part of the SFB/CRC 1709 “Cellular Plasticity in Myeloid Malignancies: From Mechanisms to Therapies. In this CRC we will focus on myeloid malignancies as a model to dissect the various molecular mechanisms that enable and regulate cancer cell plasticity in AML. Our overall goal is to pave the way for new cancer therapies.

In our project we want to decipher the niche-related adaptive molecular mechanisms that underlie and promote the emergence of FLT3-inhibitor resistant clones. The aim of this PhD position is to investigate primary cells, PDX and cell line models, and use a variety of methods to specifically identify adaptive changes in untreated, treated and drug-resistant cell populations, as well as niche-related phenotypic alterations upon drug resistance and their underlying mechanisms and pathways. These methods will include various assays to assess for intercellular interaction and migration, CRISPR-based perturbation-of-adhesion and synthetic lethality screening, drug synergy assays, and others. The PhD student wants work together with a PhD student in the lab of Prof. Jeroen Krijgsveld, which will focus on the proteomics part of the joint SFB/CRC applying project state-of-the-art proteomic approaches, e.g. low-input/single-cell proteomics, nascent proteomics, phosphoproteomics, etc. Job ID: V000014485 Field of application: Department of Hematology, Oncology and Rheumatology Location: USA Job Category: Science and teaching Working hours: Part time (65 %) Limitation: Temporary (2 years with option of extension) Contract:

CRISPR/Cas9 perturbation-of-adhesion and synthetic lethality screens Cell adhesion, trans-well migration and MSC co-culture experiments for primary AML cells and AML cell lines; generation of samples for proteomics analysis Data integration and analysis, including transcriptomic, proteomic and library screen data Target validation by CRISPR-Cas9 knockouts in primary AMLs and AML cell lines and drug/ response/synergy in-vitro assays Close collaboration with PhD student in lab of Prof. Krijgsveld who will focus on the proteomics part of the project. Possibilty to get in-depth experience in state-of-the-art proteomics approaches Close collaboration within CRC for PDX in-vivo experiments, both for investigation of mechanisms underlying niche-related drug resistance and to assess leverage points identified in this study

Master degree (or similar) in molecular biology, biomedicine, biotechnology, bioinformatics or a related field Experience in molecular biology methods (e.g. PCR, NGS, cell culture) and/or functional cell assays Interest in translational leukemia research and innovative omics technologies Bioinformatics experience, e.g. R, preferred

Goal-oriented, individual training and development opportunities Working with the latest techniques Possibility of doctorate Possibility to publish scientifically is offered and supported Regular team meetings Close collaboration within a large research consortium Collectively agreed remuneration, attractive company pension scheme (VBL) 30 days vacation Sustainable travel: job ticket Family-friendly working environment: cooperative arrangements for childcare, grant for child vacation care, advice for employees with relatives in need of care Wide range of health, prevention and sports offers Note: The UKHD is subject to the commissions of the Infection Protection Act. Therefore, a valid measles immunity certificate is required for all persons employed at the UKHD.

The UKHD embraces diversity and values diversity.

Regardless of age, gender, sexual identity, disability, origin or religion, we offer everyone the same opportunities. If one gender is underrepresented in a particular area, we place particular emphasis on counteracting this imbalance. If they have the same aptitude, qualifications and professional performance, we give priority to people severe when considering them for vacancies. JOBV1_EN