Medical Centre for Molecular Biology (MCMB) is located at the Institute of Biochemistry (IBK) of the Faculty of Medicine (MF) of the University of Ljubjana (UL). The Centre was inaugarated in February 1992, on the initiative of Prof. Dušan Sket (MF), Dr. Janez Zidar (UKC) and Prof. Radovan Komel (IBK). It was established by a consortium of institutes of the Faculty of Medicine and some clinical institutes in Ljubljana, in order to coordinate research and teaching activities in the field of medical molecular biology/genetics among institutes of the Medical Faculty, clinics of the Clinical Centre Ljubljana, and the Insitute of Oncology in Ljubljana. The signatory institutes (MCMB founders) were as follows: Institute of Biochemistry of the Faculty of Medicine (Prof. Katja Breskvar), Institute of Cell Biology MF (Prof. Nada Pipan), Institute of Biophysics MF (Prof. Saša Svetina), Institute of Pathological Physiology MF (Prof. Janez Sketelj), Institute of Pathology MF (Prof. Dušan Ferluga), Institute of Microbiology and Immunology MF (Prof. Miha Likar), Institute of Forensic Medicine MF (Prof. Jože Balažic), Institute of Pharmacology and Experimental Toxicology (Prof. Franc Erjavec), Gyneacological Clinic of the University Clinical Centre – UKC (Prof. Marjan Pajntar), Paediatric Clinic UKC (Prof. Marjan Prodan), Clinic of Endocrinology and Metabolic Diseases UKC (Prof. Andreja Kocijančič), Blood Transfusion Institute – Tissue Typing Centre (Prof. Mateja Bohinjec), Institute of Clinical Neurophysiology UKC (Doc. Miro Denišlič), University Dental Clinic UKC (Prof. Mitja Bartenjev), Psychiatric Clinic UKC (Prof. Martina Žmuc Tomori) and Institute of Oncology (Prof. Matjaž Zwitter).
The core research group of the Centre is one of the research groups of the Institute of Biochemistry of the Faculty of Medicine, formely named »Molecular Genetics Laboratory«, which in the period 1984-89 pioneered gene technology (genetic engineering) in Slovenian biochemistry and biotechnology [Komel R. et al. (1987): Construction of gene libraries of bacteria with steroid 1:2-dehydrogenase activity. Vest. Slov. Kem. Druš. 34(1): 39-52] and in 1988-90 molecular genetic analysis in Slovenian medical research and practice [Gasparini P. et al. (1990): Mutation analysis in cystic fibrosis : to the editor. N. Engl. J. Med. 323(1): 62-63].
At the begining research was performed in two main parts: (A) Biotechnology – biochemical analyis and gene cloning & expression of microbial steroid bioconverting enzymes, and (B) Medical molecular genetics – genetic analysis of monogenic diseases. As concerning part A (Biotechnology), the idea was to clone two key enzymes for steroid glucocorticoid bio-production, one from bacteria (steroid 1:2-dehydrogenase) and one from filamentous fungi (steroid 11β-hydroxylase), and join and express both proteins in a single host organism. This was a kind of »metabolic engineering«, scientific methodology preceding the modern »synthetic biology«. Namely, introduction of OH-group at 11β-position of the steroid molecule is crucial for glucocorticoid function of steroid hormones, while introduction of a 1:2 double bond into A-ring of the molecule can significantly reduce the undesired mineralocorticoid side effects. Thus, joining these two reactions would mean construction of a biotechnologically relevant microorganism. The 1:2-dehydrogenase was successfully cloned in 1993 [Drobnič K. et al. (1993): Improved purification of steroid 1:2-dehydrogenase from Nocardia opaca and partial characterization of its cloned gene sequence. Biochem. Biophys. Res. Commun. 190: 509-515], but the complex cell membrane-associated fungal 11β-hydroxylase, belonging to cytochrome P450 enzyme systems, was not. Instead of this, the CYP enzyme family was studied in detail in the context of fungal pathogen – host plant relationship, and in 2002 experimentation was substantially transfered from MCMB to the National Institute of Chemistry (partner of the joint interinstitutional program Functional Genomics and Biotechnology for Health, P1-0104; 2004 – 2014), where furthermore benzoate 4-monooxygenase (BPH) was cloned from the experimental fungus and research was then oriented to considering this cytochrome P450 as potential new target for antifungal treatment and therapy [e.g. Podobnik B. et al. (2008): CYP53A15 of Cochiobolus lunatus, a target for natural antifungal compounds. J. Med. Chem. 12(51): 3480-3486; Berne S. et al. (2012): Virtual screening yields inhibitors of novel antifungal drug target, benzoate 4-monooxygenase. J. Chem. Inf. Model. 52(11): 3053-3063].
As concerning part B (Medical molecular genetics), first genetic disease studied by genetic analysis (1988 – 1994 – 2000) was monogenic disease cystic fibrosis (CF), in collaboration with Gyneacological Clinic UKC (Prof. Srečko Rainer, Prof. Nina Canki Klain) and Paediatric Clinic UKC (Prof. Milan Štrukelj), and with beneficient support from the Medical Faculty in Verona, Italy (Prof. Pier-Franco Pignatti). In August 1990 we joined the worldwide Cystic Fibrosis Genetic Analysis Consortium and in the years to follow a systematic mutation analysis of Slovenian CF population was performed, the results shared with other European and wider populations, and molecular genetic analysis was introduced as a first molecular diagnostic procedure to our clinical institutions (i.e. Gyneacological clinic for CF). In the following years some other monogenic diseases (such as haemophilia A, adrenal hyperplasia, polycystic kidney disease, skin keratin disorders, and osteoporosis) were studied in the same way and findings translated to diagnostic procedures, education and support in building molecular diagnostic laboratories at clinical, research and university institutions. In addition, together with the Institute of Forensic Medicine at the Faculty of Medicine we also pioneered population genetic analysis and genotyping for individual identification (2001 – 2005). However, from 2000 great part of research gradually moved to more basic research on molecular basis of complex diseases such as psychatric disorders (eating disorders, suicide) and cancer (lymphoma, gastric adenocarcinoma, HNPCC, glioblastoma). In the last period (from 2010) functional genomic approach (transcriptomics, proteomics) as well as global SNP analysis & GWAS were introduced to the study of molecular roots of cancer, and to the study of genetic background of suicidal behavior. Recently, the bulk of research is focused to the search of proteomic biomarkers of cancer stem cells by using the nanobody-based reverse proteomics approach.