Research technician - Multiple myeloma immune-metabolic profiling

Multiple myeloma (MM) is characterized by a broad range of immune evasion strategies, that result in abnormalities in immune cell (and particularly T-cell) responses. Cumulative exposure to several anti-MM drugs reduce T-cell numbers or induce functional T-cell defects. In addition, increasing evidence suggests that the MM microenvironment, which consists of several components, including BM stromal cells (BMSCs), immune suppressor cells and immunosuppressive molecules, promotes tumor growth, impairs immune responses and limits the efficacy of anticancer treatments including T-cell redirecting bispecific antibodies.

So far, in depth understanding of the local and systemic immune dynamics during treatment with conventional flow cytometry has been restricted by the limited number of markers that can be detected simultaneously, imposing the need for large amount of input material. Most importantly, however, current immune profiling methods do not address the actual immune cell functional status.

Recently, it became clear that virtually all aspects of immune cell function, including differentiation, migration and secretion of immunomodulatory molecules, are regulated by dynamic changes in cellular metabolism. As an example, glycolysis has a crucial role in T cell effector function as well as in the immuno-stimulatory activity of antigen presenting cells, while fatty acid oxidation controls the development of regulatory T cells and tolerogenic dendritic cells. Importantly, recent groundbreaking studies revealed that the metabolic status can functionally discriminate T cell subsets sharing common phenotypic features that cannot be resolved using traditional markers. This underscores the potential of immune-metabolic profiling to uncover the immune dynamics that preclude effective antitumor immunity, and provide new insights into strategies to improve therapy response.

The immune-metabolic profiling team you will be part of will:

1) Biobank blood and bone marrow samples from patients with multiple myeloma undergoing therapy with T cell-redirecting agents.

2) Use cutting-edge spectral flow cytometry and cellular and molecular biology techniques, to:

• determine how tumor cells influence the blood and bone marrow immune landscape and functional status in multiple myeloma;
• explore the alterations of the blood and bone marrow immune environment induced by anti-MM therapies (with a focus on T-cell redirecting bispecific antibodies)
• explore which factors predict durable response or MRD-negativity;
• study the mechanisms underlying immune alterations with a particular focus on communication mediated by extracellular vesicles (EVs) using relevant in vitro 3D systems.

Your primary responsibilities, although not restricted to, will be to isolate cells from blood and bone marrow samples of patients with multiple myeloma and to support the spectral flow cytometry analysis of the samples. You will also be involved in organizational task including database generation and maintenance.

We seek a highly motivated research technician who possesses excellent communication skills and is able to function well in a team.

On a daily basis, we receive varying amounts of patient material from multiple hospitals, Universities and institutes all over Europe. One of your main activities involves cell isolation from incoming patient (blood and bone marrow) samples. Moreover, you will be involved in the organizational part of the study, such as biobank management and contact with external colleagues. Therefore, you are well organized, consistent and extremely reliable in the lab. Furthermore, you will work in close collaboration with a young, active international research group and thus you feel comfortable with an international cross-disciplinary environment.

As an enthusiastic research technician you also have the following qualifications:

• Strong commitment and experience with patient sample (blood and bone marrow) processing;
• Experience with flow cytometry, cell culture, and molecular biology techniques is appreciated;
• Fluency in spoken English and proficiency in writing are recommended.