(12.08.2021) The Austrian Science Fund (FWF) awards four scientists from St. Anna Children’s Cancer Research Institute (St. Anna CCRI) with Stand Alone Grants, each of which is worth almost € 400,000. Congratulations to the grantees Kaan Boztug, Eva König, Thomas Lion, and Eleni Tomazou!
Getting a Stand-Alone Project approved from the Austrian Science Fund (FWF) is what every basic scientist in Austria strives for at least once. This program successfully fulfills the FWF’s mission of providing a solid foundation for basic research at the highest level in Austria. Thus, Stand-Alone projects are an important cornerstone of the scientific work at St. Anna CCRI, an organization solely financed by donations and grants from national and international funding bodies. We are therefore proud to present four FWF projects from St. Anna CCRI scientists.
Unraveling the killing function of immune cells
In their recently approved Stand-Alone Project, Assoc.-Prof. Kaan Boztug, MD, Scientific Director of St. Anna CCRI, and co-authors Artem Kalinichenko, PhD, Senior Postdoc, and Alexis Lomakin, PhD, Program Leader & Deputy Lab Head in Kaan Boztug's group, aim to investigate the role of a small GTPase in coordinating the killing function (i.e., cytotoxicity) of immune cells. They have recently discovered an essential role for this protein for the cytotoxic function of human lymphocytes mediated through its capacity to control both the actin cytoskeleton and the exocytosis machinery. Exocytosis is used by specific immune cells to release cytotoxic molecules to attack and kill infected or tumor cells. “Discovering the specific mechanisms through which the identified protein controls and coordinates the actin cytoskeleton and exocytosis in space and time is the main goal of our project,” explains Kaan Boztug. He is convinced that the outcome of this project will directly contribute to the understanding of the molecular mechanisms of inborn errors of immunity. Furthermore, it might predict potential therapeutic avenues for such disorders.
Potentiating natural killer cells to fight cancer
Another FWF Stand-Alone grantee, Eva König, PhD, Principal Investigator at St. Anna CCRI, is investigating mechanisms that inhibit the function of natural killer cells (NK) in order to find novel ways to improve their cytotoxic capacity. Ultimately, this project aims to find immunotherapeutic agents to fight against cancer more efficiently.
In recent years, new anti-cancer therapies such as immunotherapy with natural killer (NK) cells, have reached the clinics and shown promising results. However, oncologists are still facing challenges caused by resistance to therapy and secondary metastasis. In order to find more potent and long-lasting therapeutics against cancer it is essential to determine the signaling events that are induced in NK cells upon their recognition of tumor or infected cells and that are required for effective target cell elimination. The transcription factor STAT1 plays a key role in NK cell function, regulating fundamental aspects such as cell maturation and cytotoxicity. Eva König and colleagues previously suggested a transcription-independent function and so far unrecognized involvement of STAT1 in the immunological synapse of NK cells – a discovery, which will be investigated further in this project.
Bacteria and fungi: Two partners in crime
In their Stand Alone project, Prof. Thomas Lion, MD, PhD, MSc, Medical Director of Labdia Labordiagnostik and Principal Investigator at St. Anna CCRI, and colleagues investigate polymicrobial infections involving bacteria and fungi. They aim at identifying biomarkers for diagnostics to detect these infections early. To date, interactions between bacteria and fungi in the context of invasive infections have not been widely addressed. Neither are current diagnostic approaches designed to routinely assess infections by more than one pathogen. The presence of bacterial-fungal co-infections may therefore be missed. However, polymicrobial infections are of paramount importance because of the potential severity of clinical manifestations, often associated with increased resistance to antimicrobial treatment.
Interplay of Oncogenic Fusions and Cellular Context in Sarcoma
The FWF Stand Alone Project of Eleni Tomazou, PhD, Principal Investigator at St. Anna CCRI, tackles a fundamental question in cancer biology: Why and how do certain oncogenic driver genes promote cancer in one cellular context but not in another. It focuses on fusion oncogenes relevant to sarcoma. Despite intensive research, the mechanism how fusion-driven sarcomas are induced and the cells of their origin remain unresolved until today. Together with her team, Eleni Tomazou will combine pluripotent stem cell differentiation with forced expression of sarcoma-linked fusion oncogenes, single-cell analysis, and functional perturbation experiments, to systematically probe the cellular contexts and molecular mechanisms of fusion-driven sarcomagenesis in human cells. This project will not only lead to new molecular insights into fusion-driven carcinogenesis but could also help to identify cell context-specific therapeutic vulnerabilities.
FWF Stand Alone Projects:
Identification of a key molecular coordinator of the exocytosis machinery and cytoskeletal dynamics essential for human lymphocyte cytotoxicity
Applicant: Assoc.-Prof. Kaan Boztug, MD, St. Anna Children’s Cancer Research Institute (St. Anna CCRI) & Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD)
Non-canonical STAT1 signaling in natural killer cells
Applicant: Eva Maria König, PhD, St. Anna Children’s Cancer Research Institute (St. Anna CCRI)
Characterization of Bacterial-Fungal Interactions: a Basis for Discovery of Microbial Biomarkers (BacFun)
Applicant: Prof. Thomas Lion, MD, PhD, MSc, St. Anna Children’s Cancer Research Institute (St. Anna CCRI)
Interplay of oncogenic fusions and cellular context in sarcoma
Applicant: Eleni Tomazou, PhD, St. Anna Children’s Cancer Research Institute (St. Anna CCRI)