"JOINING FORCES IN A LARGE-SCALE PROJECT FOCUSED ON EXCELENT SCIENCE WILL EXPAND OUR OPPORTUNITIES IN FUTURE"

Research teams of the ENOCH project were formed from researchers of the existing research teams of all Czech project partners: The International Clinical Research Centre of St. Anne’s University Hospital in Brno (FNUSA-ICRC), The Institute of Molecular and Translational Medicine of Palacký University Olomouc (IMTM), University Hospital Olomouc (FNOL), Regional Centre for Applied Molecular Oncology of Masaryk Oncology Institute in Brno (RECAMO) and Blood Cancer Research Group of University of Ostrava (BCRG). Teams are working within four main research programmes led by one main coordinator, Dr. Gorazd Stokin. Applicant and partner institutions are represented by experts in the field of Ageing and cancer; Ageing and chronic inflammation; Degenerative processes in ageing; Modulation of ageing, where each of these teams is completed by further researchers with general research skills (core facilities), participating in more than one group.

Research programme 1 - Ageing and Cancer

This research program addresses key aspects of underlying mechanisms of ageing and cancer and translate new knowledge into opportunities for novel preventive, diagnostic and therapeutic strategies.
Research proposed by FNUSA-ICRC in the Ageing and Cancer Research Program contributes to the topics of p53 signaling, drug resistance, stem cell differentiation, in ageing and cancer and in premature ageing of cancer survivors. Overall, research proposed in the ENOCH project strengthen and develop further translational cancer research. Great contribution to the project activities is a collaboration with experts in stress response in cancer from RECAMO, with experts in amyloidosis from University of Ostrava and with the world-renowned authority in cancer research Dr. Jiří Bártek from IMTM, who is leading the Ageing and Cancer Research Program. Research proposed within the ENOCH project is directly linked to the IMTM research program 1 – Molecular basis of diseases and molecular targets (http://www.imtm.cz/research-programs). Within this IMTM research program, researchers aim at identification and description of metabolic pathways, signaling pathways, genetic and epigenetic changes causing human diseases, particularly focusing cancer, inflammatory and infectious diseases with ultimate goal to identify new molecular targets and biomarkers for further development of new drugs and diagnostics. Therefore, the ENOCH project is highly complementary to current IMTM research agenda, it will fuel current developmental pipeline (http://www.imtm.cz/product- pipeline) with new ideas potentially leading to innovative products in the emerging field of ageing.

Research Programme I is divided into 4 research goals with corresponding specific aims.

RESEARCH GOAL 1: ASSESSING THE ROLE OF AGEING IN STRESS RESPONSE IN CANCER
RESEARCH GOAL 2: AGEING IMMUNE RESPONSE AND CANCER
RESEARCH GOAL 3: CANCER AND MODELS OF PREMATURE SENESCENCE
RESEARCH GOAL 4: PROBING THE ROLE OF CANCER IN PREMATURE AGEING

Research programme 2 – Ageing and chronic inflammation

Research proposed in Research Program II, Ageing and Chronic Inflammation, is addressing important and actual questions how chronic inflammation influences the process of ageing. The research program combines basic research approaches together with strong clinically oriented project goals. Ageing and Chronic Inflammation programme aims to understand molecular mechanisms of inflammation induced ageing and correlate such findings in clinical setting in number of different inflammation driven diseases. This Research Program is led by Dr. Danuta Radzioch who is the internationally recognized scientist in the field of inflammation. Proposed research involves an international highly collaborative group of investigators from the FNUSA-ICRC and IMTM with interdisciplinary expertise and support in basic and translational cancer research.

Problems addressed in Research Program II, are focused on molecular, cellular and clinical aspects of relationship between ageing and chronic inflammation, Research Programme II is divided into 4 research goals with corresponding specific aims.

RESEARCH GOAL 1: CHRONIC INFLAMMATION INDUCED PREMATURE AGEING
RESEARCH GOAL 2: INFLAMMATION AND ANTI-INFLAMMATORY THERAPY-INDUCED PREMATURE AGEING
RESEARCH GOAL 3: CHRONIC MICROBIAL INFECTION-INDUCED INFLAMMATION DURING AGEING
RESEARCH GOAL 4: CLINICAL ASSESSMENT OF CHRONIC INFLAMMATION AND PREMATURE AGEING

Research programme 3 - Degenerative processes in ageing

The research proposed in Research Program III, Ageing and Degeneration, is focused on molecular, cellular and clinical aspects of the relationships between degenerative processes and ageing. To significantly advance our understanding of age-related degenerative disorders we here propose translational medical research, which will allow us to gain novel insights into degenerative disorders by translating clinical findings into basic research and vice versa.

In brief, here proposed research takes advantage of well-established patient cohorts and databases, cutting-edge diagnostic modules, including innovative methods for registration and analysis of human signals, modern patient-derived tissue and stem cell approaches, animal models of degenerative disorders, advanced microscopy and high-throughput biochemistry set-ups as well as computational tools to allow modelling of disease mechanism.

These methods altogether will allow us to gain knowledge about degenerative disorders ranging from identifying early clinical features to understanding mechanistic changes at a molecular and cellular level. The combination of clinical studies and basic research methods, in particular, will open new vistas in understanding pathogenesis of degenerative disorders and allow for novel diagnostic and therapeutic approaches.

This Research Program is led by Dr. Jiří Damborský who is internationally recognized scientist in the field of protein chemistry. The proposed research involves an international highly collaborative group of investigators from the FNUSA-ICRC, IMTM and FNOL with interdisciplinary expertise. The Research Programme is divided into three research goals with corresponding specific aims.

RESEARCH GOAL 1: PROBING MECHANISMS OF AGE-RELATED DEGENERATION
RESEARCH GOAL 2: IDENTIFYING EARLY CLINICAL FEATURES OF DEGENERATION
RESEARCH GOAL 3: MODULATING DEGENERATION DURING AGEING

Research programme 4 - Modulation of ageing

The ENOCH RP4 is focused on research of new therapeutic and diagnostic strategies to approach age
related diseases. Research proposed within the ENOCH project is directly linked to the IMTM RP2-Medicinal chemistry, RP3-Chemical biology and experimental therapeutics, RP4-Biomarkers -identification and validation, RP5-Pharmacology and toxicity and RP6-Translational medicine (http://www.imtm.cz/research-programs), which are organized around development pipeline of prototypical medicinal products (e.g. small molecules/drugs, biomarkers/diagnostics and medical devices) providing expertise needed for translational proof-of-concept studies.

This Research Program is led by Dr. Marian Hajdúch (IMTM) who is internationally recognized expert in the field of identifying and testing biologically active molecules and identification/validation of novel biomarkers. Proposed research involves an international highly collaborative group of investigators from IMTM, FNUSA-ICRC and FNOL with multidisciplinary expertise in drug development and innovative diagnostics. This work program is complementary to the other ones since it provides opportunities to translate new discoveries into medicinal products. Research proposed in Research Program IV, Modulation of Ageing, explores novel basic mechanisms and interventions to ageing.

Research is divided into 2 research goals with corresponding specific aims.

RESEARCH GOAL 1: EXPLORING SENOTOXIC ACTIVITIES
RESEARCH GOAL 2: ENHANCING APPROACHES TO AGEING

Involvement of the foreign strategic partner - The McGill University Health Centre (MUHC)

Strategic foreign partner for the ENOCH project is the Research Institute of the McGill University Health Centre (RI-MUHC). It was identified based on long-term collaboration with IMTM researchers, scientific excellence in most of the ENOCH research topics, strong training and education, high-end infrastructure, unique experience in technology transfer/business development, premium reputation for health care and very good link to pharma and biotech industry. The collaboration with research groups of RI-MUHC will further expand to other research teams on both Canadian and Czech site. Within the ENOCH project RI-MUHC is involved in activities of all research programmes.

Involvement of the foreign strategic partner - The Mayo Clinic

The Mayo Clinic partner was identified based on long-term collaboration between FNUSA-ICRC and Mayo Clinic and scientific excellence of the Mayo Clinic cancer biology team, as well as its complementary nature with the ENOCH research topics. The collaboration will expand to other research teams on the Czech side and will provide strong training and education to the ENOCH team members, access of the U.S. members to high-end infrastructure built in Moravia in the past years, and unique experience in technology transfer and a very good link to pharma and biotech industry for the Czech teams. Researchers involved in collaborative projects will have opportunity to benefit from Mayo Clinic experience and from new state-of-the-art facilities in Brno, Olomouc and Ostrava (FNUSA-ICRC, IMTM, RECAMO and BRCG-UO) to conduct basic and applied research. Within the ENOCH project Mayo Clinic is involved in activities of all research programmes.

Involvement of the foreign strategic partner - University of Queensland

As part of the project activities, cooperation with the University-wide Center for Stem Cell Aging and Regenerative Engineering (UQ-StemCARE) was initiated. The partner will be actively involved in already implemented proposed studies focusing on aging, such as activities such as internships, joint participation at foreign conferences, sharing know-how and experience, writing joint professional publications, etc. All activities will be coordinated by the partner by Prof. Justin Cooper-White, and any further future cooperation will be managed by mutual agreement between the two parties.