University Zurich ()

University of Zurich is one of the top universities in Europe with 26,472 students studying at 7 faculties and an annual budget of 1.377 billion Swiss francs. UZH has a very strong research background in natural and medical sciences acknowledged with two (12 in total) Nobel prizes in Physiology and Medicine. The laboratory of one of them, Prof. Walter Rudolf Hess, has given rise to the Hypoxic lab of Prof Max Gassmann and the Red Blood Cell Research Group within it headed by Prof. Anna Bogdanova. This group of 8 researchers and PhD students is actively working to characterise the function of red blood cells of humans and the impact of stress and diseases associated with anemic state in red blood cell properties and turnover. The group is associated with clinical hematologists, physicists, and engineers to carry on ambitious multidisciplinary projects funded by national and international foundations.

Role and Commitment of key persons (including supervisors)

Within the group, the ESR will work under supervision of Prof Bogdanova (30%) and educated by the Postdoctoral fellows of the group (Dr Makhro 30% and Dr Seiler 30% as well as by the lab technician N. Bogdanov (15%)). The ESR will enroll into the imMED (Integrative Molecular Medicine) PhD program of the UZH and will attend educative program events there.

Key Research Facilities, Infrastructure and Equipment

Red blood cell research group is a part of the Institute of Veterinary Physiology at the UZH owning all the devices required for experimental work (common biochemistry, molecular biology and physiology labs. Equipment includes ABL blood analyser, Chemiluminescence NO detector, GEMOX analyser, Myrene viscosimeter, patch clamp rig, chemiluminometer and spectrophotometers, C-lab and cell culture lab with hypoxic incubators and working benches, inverted fluorescence microscopes and microfluidic system for chip perfusion to use with the microscopes, flow cytometer and CO-oximeters. All this equipment together with the Institute’s infrastructure will be available for the recruited ESR to use. In addition UZH has a shared Advanced Microscopy center and Functional Genomics center to use for all working at the UZH.

Status of Research Premises

As mentioned above, all the devices and the infrastructure needed for the project implementation are owned by the Institute to which the group belongs. They may also be used by the other consortium members whenever needed.

Previous Involvement in Research and Training Programmes

Members of the group were participating in joint projects with the Enhelgardt Institute of Molecular Biology (Moscow, Russia) and the Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (Madrid, Spain) on the investigation of the mechanisms of redox-based signalling in various cell types. Red blood cell research group is actively involved in research and training programs. The CoMMiTMenT project completed with our participation recently (European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement No 602121) integrated us into the European network that was reinforced by the RELEVANCE ITN project.The group is a part of Trialect educational network providing trainings in functional red blood cell physiology to the medical community worldwide for the past 2 years.

Current Involvement in Research and Training Programmes

Prof. A. Bogdanova is a coordinator of the currently running European Union’s Horizon 2020 research and innovation programme (No 675115 — RELEVANCE — H2020-MSCA-ITN-2015/H2020-MSCA-ITN-2015).International projects with our participation were and are currently funded by the Swiss National Science Foundation include Sinergia consortium project (Israel-Switzerland)on the development of device for detection of intraerythrocytic free and and a D-A-CH project on Neocytolysis.

Relevant Publications and/ or Research/ Innovation Product

• Fermo, E., Bogdanova, A., Petkova-Kirova, P., Zaninoni, A., Marcello, A.P., Makhro, A., Hanggi, P., Hertz, L., Danielczok, J., Vercellati, C., Mirra, N., Zanella, A., Cortelezzi, A., Barcellini, W., Kaestner, L., and Bianchi, P. (2017). 'Gardos Channelopathy': a variant of hereditary Stomatocytosis with complex molecular regulation. Sci Rep 7, 1744. • Hanggi, P., Makhro, A., Gassmann, M., Schmugge, M., Goede, J.S., Speer, O., and Bogdanova, A. (2014). Red blood cells of sickle cell disease patients exhibit abnormally high abundance of N-methyl D-aspartate receptors mediating excessive calcium uptake. Br J Haematol 167, 252-264. • Hernansanz-Agustin, P., Ramos, E., Navarro, E., Parada, E., Sanchez-Lopez, N., Pelaez-Aguado, L., Cabrera-Garcia, J.D., Tello, D., Buendia, I., Marina, A., Egea, J., Lopez, M.G., Bogdanova, A., and Martinez-Ruiz, A. (2017). Mitochondrial complex I deactivation is related to superoxide production in acute hypoxia. Redox Biol 12, 1040-1051. • Makhro, A., Hanggi, P., Goede, J.S., Wang, J., Bruggemann, A., Gassmann, M., Schmugge, M., Kaestner, L., Speer, O., and Bogdanova, A. (2013). N-methyl-D-aspartate receptors in human erythroid precursor cells and in circulating red blood cells contribute to the intracellular calcium regulation. Am J Physiol Cell Physiol 305, C1123-1138. • Petrushanko, I.Y., Yakushev, S., Mitkevich, V.A., Kamanina, Y.V., Ziganshin, R.H., Meng, X., Anashkina, A.A., Makhro, A., Lopina, O.D., Gassmann, M., Makarov, A.A., and Bogdanova, A. (2012). S-glutathionylation of the Na,K-ATPase catalytic alpha subunit is a determinant of the enzyme redox sensitivity. J Biol Chem 287, 32195-32205.