ENHANCING THE CAPACITY OF
BIOMEDICAL RESEARCH
IN BULGARIA
Molecular Medicine Center
Medical University - Sofia
www.mmcbg.org
Background
Why here?
Medical University Sofia is the leading
medical education institution in Bulgaria
The growing interest of Bulgarian clinical
specialists in the molecular factors
contributing to common inherited disorders
 National Genetic Laboratory for diagnostics
and control of inherited disorders
Strategic aim
To enhance Bulgaria’s capacity and potential
for biomedical research in the field of
molecular medicine
By
Establishing a collaborative, multidisciplinary
Molecular Medicine Centre (MMC)
at Medical University of Sofia
Objectives






Reinforcing the technological and scientific potential
in Biomedical sciences
Supporting excellent research in molecular medicine
Expanding expertise in molecular genetics and
genomic research
Establishing networks with research centers in
Bulgaria and EU for collaborative studies
Dissemination of scientific knowledge and information
Response to the socio-economic demands of Bulgaria
MMC - Phase I

2004 FP6 Specific Support Action
“Integrating and Strengthening the European Research Area” Promotion of co-operation
with Associated Candidate Countries contract INCO-CT-2005-017147, 2005-2008
Financial contribution of EC: 998 880 €

2006 NSF funded infrastructure project DRI-15/2006-2008
“Establishing SNP genotyping and gene expression Core facility at MMC, MU-Sofia”
Financial contribution of NSF 252 607 €

2008 NSF funded infrastructure project CVP01/0123 (2008-2010)
“Enhancing the research potential of Medical University of Sofia, through establishing the
collaborative, multidisciplinary Molecular Medicine Centre as a major national research
infrastructure in the field of biobanking, functional genomics, proteomics and
metabolomics”
Financial contribution of NSF 1 534 056 €
Personalized Medicine
Transfer of the fundamental research to the patient’s bed
Research
Diagnostics
& Treatment
Clinic
Personalised Medicine
Transfer of the fundamental research to the patient’s bed
Research
Clinic
MMC
Diagnostics
& Treatment
Strategy for Development
Improved Health Care and
Quality of Life
Contacts with
Pharmaceutical
and other
industry
Patenting
Modern
Infrastructure
Modern
Technologies
Education in
molecular
medicine
Fundamental
Research
Clinical and application oriented
research
Structure and Management
Advisory Board
Scientific Board
Financial control
Management Committee
Research
Groups
MMC
Cores
Research
Groups
Administration
MU - Sofia
Research
Groups
MOLECULAR MEDICINE CENTER
Sources of Financing
- EC funding
- National Science Fund, Ministry of Education
and Science
- Medical University Sofia – Research Fund
- Industry , foundations, etc
Stages of project implementation
Technological core facilities – Phase 1
1
2
3
Biobanking
Genomics
Bioinformatics
DNA
Plasma
Urine
Tumors
Stem cells
DNA sequencing
Gene expression
Genotyping
Access to
databases
Statistics



Up-to-date technology
platforms for efficient,
high-quality and cost
effective genetic analysis
Local computer network
providing access to
databases and software
Increased capacity of
isolation and long term
storage of biological
probes for all
researchers in
MU-Sofia
Technological core facilities – Phase 2
4
5
6
7
Microarrays
Laser
microdissection
Metabolomics
Cell culture
Genetic
Genomic
Epigenetic
analysis
Single or few
cell isolation
for further
analysis
Profiling and
analysis of
small
substances in
biological fluids
Cell and tissue
cultures
EBV
transformation


Useful for diagnostics,
therapy and
investigation of
molecular events in
cells
Assisting the
enlargement and
diversity of our
biobank collection

Up-to-date
technology for
efficient, highquality analysis

Fostering the research
and quality of isolated
cells for subsequent
use in functional
genomics and
proteomics studies
Phase 1- Biobanking
Provides



Automated DNA/RNA isolation
Measurements and normalization of DNA samples
Long term archive of biological fluids and tissues (cells, tissues, plasma, serum, urine
DNA/RNA)
Equipment





CHEMAGEN automated modul for DNA isolation
Liquid Handling Robot BIOMECK FX, Beckman
700 l Deep freezers at -80 oC Forma ULT,
Freezers at -20 oC,
Liquid nitrogen Duar vessels
Phase 1- Genomics
Provides
Wide range of genomic
technologies
Expert help, technical assistance







Sequencing
Fragment analysis
Gene expression
SNP genotyping
MLPA
DNA Methylation
Q-PCR
Equipment





Genetic Analyser ABI3130xl
ABI Prism 7900 HT RT-PCR
NanoDrop spectrophotometer
Photodocumentation
Standard Lab equipment
Phase 1- Bioinformatics
Provides
 Access to databases
 Storage of project data
 Specialized software
 Expert help in project design
 Data analysis and interpretation
Equipment






Intranet with 15 computer
workstations
File server
Database server for genetic and
clnical data
Application server
LIMS (Nautilus Thermo Scientific)
Firewall
Phase 2 -Microarrays
Provides
 Gene expression profiling
 CGH arrays
Equipment
 Hybridization oven
with 24 slides capacity
 SNP detection
 Fusion gene microarray
 Microarray based DNAmethylation profiling
 Analysis of siRNA, miRNAs
 Agilent Laser array
scanner with carrousel
for 48 slides
Phase 2 - Laser microdissection
Provides
 Isolation of single cells from
large areas of frozen tissues or
from paraffin embedded materials
Equipment
 Palm
MicroBeam
Laser
Microdissection
system, Zeiss
Phase 2 - Metalobolomics
Provides
Equipment MMC and NGL
 Profiling
and
analysis
of
biological fluids – plasma, urine of
patients aiming at new biomarker
detection
 Thermo LC/MS hybrid system
 Investigation of the molecular
events in cells and tissues in cancer
and/or apoptosis
 DelfiaExpress fluorescent system
 Investigation
of
possible
relationships
between
known
genomic disorders and metabolomic
profiles
 Two HPLC systems
 Investigation of nutrition in
relation to metabolism in disease
and health.
 Single quadropole
ionization
GC/MS
with
EI
 Victor D fluorescent and luminescent
system
Phase 2 - Cell culture
Provides
 Application
of
cell
biology
approaches and functional genomic
studies
for
elucidating
the
mechanisms of inherited disorders
 Enlargement and diversity to our
biobank collection, through inclusion
of cell and tissue cultures
Equipment
 2 laminar flow cabinets
 CO2 cell culture incubators
 Inverted and fluorescent
microscopes
Human Resources
Coordinator
Management
Post Docs
Bioinformatician
IT Specialist
Technicians
Research PhD students
Clinical PhD students
1
3
2
1
1
4
4
10
Research Groups







Neurogenetics
Psychiatric and behavioural
genetics
Oncogenetics
Ophalmogenetics
Pharmacogenetics and
pharmacogenomics
Population genetics
Genetics of common complex
disorder
Neurogenetics
1
DNA Bank
Clinical Registry
Hereditary
Peripheral
Neuropathies
Epilepsy
2
Molecular Analysis
Achievements
•
• DNA
sequencing
• Haplotype analysis
• Linkage
Dementia
• Expression
Parkinson
• Predisposition
Alzheimer
3
New mutations
• New clinical forms
• New Loci
• New genes
• Improved genetic and
clinical diagnostics
• Recommendations for
genetics counseling and
diagnostics
Neurogenetics
Department of Genetics
MU-Varna
Department of Pediatrics
MU-Plovdiv
Department of Neurology
MU-Sofia
Department of Pediatrics
MU-Sofia
Molecular Medicine Center
EUROPEAN CMT consortium
Funding:
European network TREAT-NMD
European and American
Patent
National Institutes of Health, USA
Muscular Dystrophy Association, USA
The Neuropathy Association of the USA
Flanders Science Fund, Belgium
National Science Fund, MES
Science Fund, MU-Sofia
Publiciations since
2005
7 Bulgarian
10 International
Psychiatric and Behavioural Genetics
1
2
DNA bank
Clinical and genetic
database
Molecular Analysis
Affective disorders
Big families
Sibpairs, Trios
Case/controls
•Association studies
•Linkage analysis
•LD and haplotype analysis
Addictions
Case/controls
Association studies
Behavioural genetics
Autism
Sibpairs, trios
Case/controls
Association studies
3
Achievements
Phenotype and Genotype
database
New linked loci
Susceptibility genes
Phenotype and Genotype
database
Phenotype and Genotype
database
Psychiatric and Behavioural Genetics
Local Psychiatrists
Bulgarian Addictions
Institute
Initiative for
Health Foundation
Department of Psychiatry
MU Pleven
Department of Psychiatry
MU-Sofia
Molecular Medicine Center
Funding
European Consortium on
affective disorders
Alexander von Humboldt Research Foundation, Germany
BIOMED1, BIOMED2 programs of EC
NIDA, USA
NHMRC, Australia
National Science Fund, Ministry of Education and Science
Science Fund, MU-Sofia
Publications
18 international
5 Bulgarian
Oncogenetics
Biobanking
Molecular
Genetics
HNPCC
MSI
Methylation
Sequencing MLH1/2
MLPA
DNA Tumor Plasma
FAP
Endometrial
Cancer
Breast Cancer
BRAF analysis
Prostate Cancer
Sequencing
BRCA1/2 genes
Larynx Cancer
Brain tumors
Register of Familial
Cancer
SNP genotyping Association studies
Gene Expression
Diagnostics and
Prophylactics
Genetic Counseling
Carrier testing
Targeted therapy
Oncogenetics
Department Pathology
Trakia University,
St.Zagora
National
Oncological
Institute
Univ.
Hospital
“Pirogov”
MU Sofia
Clinical Center GAstroenterology
UH “Tzarica Joanna”
MU-Sofia
Univ.Hospital
“Maichin Dom”
MU-Sofia
Molecular Medicine Center
Dr. Markku Vaarala,
Department of Pathology,
University of Oulu, Finland
Financing
IMPACT, PRACTICAL,
Prof. R Eeles,
ICR, Sutton, UK.
Program “Research Capacity”
National Science Fund, MES
Science Fund, MU-Sofia
МБАЛ “Св. Марина”
MU-VArna
FP7, REGPOT
Prof. J. Lubinski,
Pomeranian Medical University,
Poland.
Publications 2005 г
3 Bulgarian
4 International
Ophtalmogenetics
1
2
DNA Bank
Clinical database
Molecular Analysis
Retinitis Pigmentosa
• Linkage analysis
• Haplotype analysis
• DNA sequencing
Congenital Glaucoma
DNA sequencing
Age Related Macular
Degeneration
Association study
AMD
3
Achievements
• New mutations
• Genotype-Phenotype
correlations
New mutation
Genetic tests
Ophtalmogenetics
Department of Neurology
MU-Sofia
Foundation
Minority Health Problems
Institute of Ophtalmology
London
Department of Ophtalmology
MU-Sofia
Molecular Medicine Center
Financing
National Program Genomics
National Science Fund
Science Fund, MU-Sofia
NHMRC, Western Australia
Publications
1 Bulgarian
3 International
Pharmacogenetics
Department
Biochemistry
MU-Sofia
MU-Plovdiv
MU-Pleven
Central Lab of Drug
monitoring and clinical
pharmacology
National Cardiology Hospital
Department Clinical
Pharmacology
MU-Sofia
Molecular Medicine Center
Financing
National Science Fund, МОН
Science Fund, MU-Sofia
Science Fund, MU-Pleven
University of Lausanne,
Switzerland
Publiciations
1 Bulgarian
1 International
Education





Courses in molecular medicine for medical
students
Courses in molecular pathology and genetics
for biology students
Specialised training for postgraduate
students
Technological basis and scientific
supervision for MSc and PhD students in
molecular biology and genetics
Expert help to researchers
Local Networking
MMC
Nutrigenomics Centre
MU Varna
Genome Centre for
Common Diseases
MU Sofia
Bulgarian Academy
of Sciences
Sofia University,
Faculty of Biology
AgroBioInstitute (ABI)
Centre of Excellence in
Plant Biotechnology
Medical Universities
in
Pleven, Varna, Plovdiv,
Stara Zagora
SMEs & NGOs
Molecular Medicine Center
International Networking
Flanders Interuniversity Institute
of Biotechnology, Belgium
Life & Brain Centre,
Bonn, Germany
Microarray Core
Facility (MAF), VU
University Medical
Centre/ Cancer Centre
Amsterdam
Washington University
St. Louis, USA
MMC
CMM
Edinburgh, UK
IHCRC
Poland
University of Western Australia
Institute of Ophtalmology,
London, UK
Molecular Medicine Center
Dissemination of knowledge







MMC web site
Journal Subscriptions
Regular Seminars
Open Door Days
National Consultative meeting
“Molecular medicine in Bulgaria:
Prospects and Challenges” 2008
Workshops with media
“Ethical aspects of genetic
research”
Research conferences
MMC
Sustainability and Financing
Projects 2005 г
4
6
Projects 2009 г
8
6
13
International
NSF
8
SF-MU-Sofia
MMC – Scientific profile
25
20
15
10
MMC&NGL
BIOCHEMISTRY
&MMC
5
0
2000
2002
2004
2006
2008
Publications of MMC, NGL and the
Department of Biochemistry, MU- Sofia
Molecular Medicine Center
key aspects
 Attractive technology platform in the region
 Partner in national and international networks
 Strong multidisciplinary center for excellent
molecular medicine research
 Translational oriented research
 Impact on public health, diagnostics, treatment
Molecular Medicine Center
Phase 3

National Centre of Excellence in Functional genomics, metabolomics
and proteomics

National University Complex in Biomedical
and Translational Research
200 scientists
30% young scientists
2 Medical Universities
.
Towards MMC –Phase 3
2008-2010

National program for Centres of excellence
“Molecular Medicine Centre (MMC) as a major national research infrastructure in the
field of biobanking, functional genomics, proteomics and metabolomics”.,
PI Prof. V. Mitev, Project CVP01/0123 (2008-2010), Contract DO02-118/2008
NSF, Ministry of Education and Science (90%) and MU- Sofia (10%)
Total Budget
1 534 056 Euro
of which for Equipment
1 187 446 Euro
2010-2015
 Project University Research Complex
URC01_03/ 2010-2015
PENDING!!!!
“University Complex for biomedical and translational research”
NSF, Ministry of Education and Science (90%) and MU- Sofia (10%)
Total Budget requested:
~ 15 000 000
Euro
of which for equipment for the CoE
3 306 015
Euro
Create research clusters
MU –Sofia and Plovdiv






New research cores
Neuroimaging Core, MU-Sofia
Microscopy Core, MU- Sofia
Research core at Faculty of Pharmacy, MU-Sofia
Research complex for Molecular Biology and Immunology, MUPlovdiv
Upgrade existing cores, especially Bioinformatics
Create national network for biobanking resources
Upgrade of facilities for fundamental research in Biology,
Microbiology, Pharmacology, Physiology
Enhance capacity for clinical research at University Hospitals
Increase capacity of existing central laboratories for
translational research
National Genetic Laboratory
Clinical Immunology
Central Laboratory for Drug Monitoring and Clinical
Pharmacology
National University Complex for
Biomedical and Translational Research
MF, MU-Sofia
24 departments
PF, MU-Sofia
5 departments
MF, MU-Plovdiv 3
departments
9 University
Hospitals and
2 National Centers
Budget justification

Total budget requested ~ 15 000 000 Euro for 4 years project
90 % from NSF, Ministry of Education, Youth and Science
10 % from MU-Sofia and MU-Plovdiv









Equipment
69 %
Consumables
8 %
Software
1 %
Operational costs
3 %
Human resources
7 %.
Networking and Training
5 %
Dissemination
1 %
Indirect costs
6 %
New core facilities renovation and furniture – from the
budget of MU-Sofia
National Network
MMC – part of ERA
 Participation in European Consortia
 Networks and joint research with similar European
Research Centers
 Regional Networking with Western Balkans in
particular
 Exchange of know-how, training and research visits
 Joint PhD supervision
 Participation in European research projects