INNOVATION statement

Only recently, it became clear that ion channels and the membrane potential of red blood cells (RBCs) are highly relevant for human physiology and medicine; this includes the general scientific understanding of how RBCs are formed, how they survive, and how they influence physiological conditions going far beyond the blood. These ion channels function independently alongside carriers like anion exchanger Band3 (AE1/SLC4A1) or ion pumps. Of note, the 2021 Nobel Prize for Physiology or Medicine was awarded to research on mechanosensing PIEZO ion channels, which are abundant on the RBC membrane, next to Ca2+-dependent Gárdos channels (KCNN4). Understanding the regulation of ion transport is urgently needed for diagnosis and treatment of RBC-related diseases: globally, one quarter of the world’s population suffers from anaemia and rare and congenital anaemias are increasingly recognized to be a major health problem. The large-scale in vitro production of RBCs with tailored properties can revolutionize transfusion medicine. Investigating and manipulating RBC ion-conducting properties bears the opportunity to treat numerous (initially unrelated) diseases by novel concepts of targeted drug delivery for gene therapy.

About Sanquin

Sanquin’s mission is: “Together with the donor we ensure a better life for patients”. We are a knowledge-driven not-for-profit organization that supplies life-saving products and services, and focusses on blood transfusion medicine- and immunology-related research. This research is performed by a dedicated staff and is organized in  four medical priorities, i.e.: Anemia, Bleeding and Hemostasis, Immunotherapy, and Immunity and inflammation. Sanquin’s research portfolio covers a broad spectrum ranging from basic to applied and clinical research and product- and process development. Sanquin provides a lively, internationally oriented, scientific environment with excellent facilities. We also organize weekly scientific meetings, journal clubs and work discussions to gain scientific input and to exchange knowledge. Importantly, being part of INNOVATION entails participating in exchange programs between partners, regular consortium meetings and plenary training programs organized by the different partners.

The project

We are looking for a highly motivated master graduate, who will be working in within the medical priority Anemia and as part of INNOVATION. Sanquin research contains several groups that study hematopoietic stem cells support by mesenchymal stromal cells, T-cell differentiation and activation, and the molecular mechanisms that control erythropoiesis. Specifically in my group, Dr. Emile van den Akker, we routinely generate and differentiate various hematopoietic/blood cell types from a range of sources including iPSC. Understanding the role of ion channels and ion homeostasis in various developmental stages of RBCs can provide important insight into the mechanisms of channelopathies that are linked to anaemia, in in vitro erythropoiesis in stirred bioreactors, and ultimately in the role of membrane potential in non-excitable cells in general. Each single ion channel whose expression is detected in RBC precursors will be deleted to assess how specific channels contribute to proliferation and maturation of RBC precursors and to RBC function. This will be complemented with conditionally (over)expression of wild-type or mutant channel proteins. We will thus assess whether aberrant expression affects proliferation or differentiation of RBC precursors or the function of mature RBCs. The research will include understanding the contribution of specific mechanosensors to erythropoiesis and to the production of cultured red blood cells in large bioreactor settings. We have 500ml to 3liter 3D printed bioreactor setups that will be available for this project. A range of different molecular techniques will be applied (e.g. flow cytometry, automated patch clamp, imaging), in addition to bioinformatic analysis of large datasets. The position includes but is not limited to extensive cell biology (including primary erythroid cultures), general biochemical approaches, various omics (metabolomics/proteomics), fluorescence-based techniques including imaging. The successful completion of this project will result in a better characterization of erythropoiesis, which consequently is expected to increase the quantity and quality of in vitro produced erythrocytes. It forms the basis of future experiments to model channelopathies in health and disease while also allowing to interrogate the effect of various permutations and/or insults (systemic or not) on erythroid formation and functionality.

Your profile

A master in cellular and molecular biology or a related discipline; experience in hematopoiesis will be a competitive advantage; an independent, responsible and team-oriented candidate; good communication and writing skills in English. The MSC doctoral network requires international mobility. We can only accept candidates that do not have the Dutch nationality, and did not reside for more than 6 months in The Netherlands before the projected start of the position.

Fixed-term contract: 3 years.

Conditions of employment

We offer unique research opportunities in a dynamic environment. Nowhere else in the world you will find an organization that combines medical, pharmaceutical, diagnostic and scientific research under one roof.  In addition to a challenging project in a multi-disciplinary and enthusiastic team we offer:

• Salary and working conditions conform CAO Sanquin;
• Temporary position (project duration of 3 years );
• A full time contract of 36 hours per week;
• 8,33% end-of-year bonus;
• 8,33% holiday allowance;
• Partial reimbursement of travel expenses;
• Pension plan with Pensioenfonds Zorg & Welzijn (PFZW), Sanquin contributes 60%;
• Collective discounts on various insurances;
• At fulltime employment (36 hours) 201 hours of leave per annum.

Learn more about our terms of employment at https://www.sanquin.org/working-at/who-we-are/employment-conditions.