KFO 326:  Male Germ Cells: from Genes to Function

• Subject Area: Medicine
• Term: since 2017
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 329621271

From Genes to Function - an Integrated Approach Male infertility is a genetically and clinically highly heterogeneous disease. Thus, unravelling the underlying causes and the pathophysiology is challenging and requires an integrated approach. To this end, we set up a Clinical Research Unit (CRU) that investigates in translational projects human male germ cell function from organ formation to sperm dysfunction at the genetic, epigenetic, and molecular level. In Münster, the setting to study male infertility is unique. On the campus, interdisciplinary expertise on the biology of male germ cells co-locates with major andrological, genetic, and stem cell institutions. Successful bilateral collaborations have already proven the potential for concerted basic, translational, and clinical research. However, to tap the full potential of this environment and to trigger synergies, it is required to intimately interconnect the institutions. Similarly, common animal models such as the zebrafish are still insufficiently used to gain insight into human male germ cell development und function. The CRU consists of three layers that are interconnected by the DNA, i.e. the concerted research on the epi-/genetics of male germ cells and the professorship of Reproductive Genetics. We joined clinical and basic research institutions that primarily study male germ cell function with institutions that primarily focus on stem cells, paediatrics, and powerful animal models to interconnect basic science (basic layer) and clinical research (top layer) by a network of research projects (connecting layer). The eight research projects are tightly interlinked and address the following unifying hypothesis: A wide spectrum of leading pathologies with the common denominator of male infertility (e.g. gonadal dysgenesis, spermatogenic failure, and dysfunction of spermatozoa) share common epi-/genetic causes. Improving phenotyping by interdisciplinary evaluation of patients, interconnecting basic and clinical research, and linking clinical to OMICs data will elucidate novel distinct pathologies and their genetic basis. The research goals will be achieved by close interaction, complementary knowledge transfer, access to the biobanks, exchange of data, and use of cutting edge technologies. Thus, this CRU breaks current barriers between disciplines as well as basic science and clinical research. It will overcome the classical concept of male infertility as an isolated disease and create an integrated view allowing both forward (gene to patient) and reverse (patient to gene) approaches to identify novel epi-/genetic factors and associated phenotypes that impact germ cell function. This will significantly improve the diagnostic yield in infertile male patients and, ultimately, improve patient care.

• DFG Programme: Clinical Research Units

Projects

• 3D genome characterisation of human spermatogenesis (Applicant Vaquerizas, Juan M. )
• Coordination Funds (Applicant Gromoll, Jörg )
• Coordination Funds (Applicant Tüttelmann, Frank )
• CP: Bioinformatic pipelines and integrated analyses (Applicants Tüttelmann, Frank ;  Varghese, Julian )
• Genomics of severe spermatogenic failure (Applicant Tüttelmann, Frank )
• Male infertility caused by defective sperm flagella beat generation due to ODA defects (Applicant Omran, Heymut )
• Modelling the developing gonad – organoid- and iPSC-based approaches (Applicant Schlatt, Stefan )
• Molecular defects in multiple morphological abnormalities of the sperm flagellum (MMAF) (Applicant Raidt, Johanna )
• Molecular mechanisms of spermatogenic failure at transcriptional and epigenetic level (Applicants Laurentino, Sandra ;  Neuhaus, Nina )
• Molecular signatures of Sertoli cells (Applicant Gromoll, Jörg )
• The molecular role of M1AP in meiotic arrest (Applicant Friedrich, Corinna )
• The (patho)physiology of ion channels in human sperm (Applicants Brenker, Christoph ;  Strünker, Timo )
• The role of the Dead end protein in controlling germ cell fate (Applicant Raz, Erez )

• Spokesperson: Professor Dr. Jörg Gromoll
• Leader: Professor Dr. Frank Tüttelmann
• Project Heads: Dr. Christoph Brenker; Professor Dr. Martin Dugas; Dr. Corinna Friedrich; Professorin Dr. Sabine Kliesch; Dr. Sandra Laurentino; Dr. Eva Mall; Professorin Dr. Nina Neuhaus; Professor Dr. Heymut Omran; Dr. Johanna Raidt; Professor Dr. Erez Raz; Professor Dr. Stefan Schlatt; Professor Dr. Timo Strünker; Professor Dr. Juan M. Vaquerizas