ENHANCING THE CAPACITY OF BIOMEDICAL RESEARCH IN BULGARIA Molecular Medicine Center Medical University - Sofia

ENHANCING THE CAPACITY OF ENHANCING THE CAPACITY OF BIOMEDICAL RESEARCH BIOMEDICAL RESEARCH

IN BULGARIAIN BULGARIA

Molecular Medicine CenterMolecular Medicine Center Medical University - SofiaMedical University - Sofia

www.mmcbg.orgwww.mmcbg.org

BackgroundBackground

Why here?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 aimStrategic aim

To enhance Bulgaria’s capacity and potential for biomedical research in the

field of molecular medicine

ByByEstablishing a collaborative,

multidisciplinary Molecular Medicine Centre (MMC)

at Medical University of Sofia

ObjectivesObjectives Reinforcing the technological and scientific

potential in Biomedical sciences SSupporting 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 Response to the socio-economic demands of

BulgariaBulgaria

MMC - Phase MMC - Phase II

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, 2005-2008Financial 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 €€

Research Clinic

Diagnostics & Treatment

Personalized Medicine Transfer of the fundamental research to the patient’s bed

Research Clinic

Diagnostics& Treatment

MMCMMC

Personalised Medicine Transfer of the fundamental research to the patient’s bed

Modern Infrastructure

Modern Technologies

Education in molecular medicine

Fundamental Research

Clinical and application oriented research

Contacts with Pharmaceutical

and other industry

Patenting

Improved Health Care and Quality of Life

Strategy for DevelopmentStrategy for Development

Scientific BoardScientific Board

MOLECULAR MEDICINE CENTER

MU - SofiaMU - Sofia

Financial controlFinancial control

AdministrationAdministration

ResearcResearch h

GroupsGroups

Management CommitteeManagement Committee

Advisory BoardAdvisory Board

Sources of FinancingSources of Financing - EC funding - National Science Fund, Ministry of Education and Science - Medical University Sofia – Research Fund- Industry , foundations, etc

Structure and ManagementStructure and Management

MMCMMCCoresCores

ResearcResearch h

GroupsGroups

ResearcResearch h

GroupsGroups

Stages of project implementation

1 2 3

Technological core facilities – Phase 1

DNAPlasmaUrine

TumorsStem cells

DNA sequencingGene expression

Genotyping

Access to databasesStatistics

Increased capacity of

isolation and long

term storage of

biological probes for all

researchers in

MU-Sofia

Biobanking Genomics Bioinformatics

Up-to-date technology platforms for efficient, high-quality and cost

effective genetic analysis

Local computer network providing access to

databases and software

Technological core facilities – Phase 2

4

GeneticGenomic

Epigenetic analysis

Up-to-date technology for efficient, high-quality analysis

Microarrays

5

Single or few cell isolation for further analysis

Laser microdissect

ion

Fostering the research and quality of isolated cells for subsequent use in

functional genomics and proteomics

studies

6

Profiling and analysis of

small substances in biological

fluids

Metabolomics

Useful for diagnostics, therapy and investigation of molecular events in

cells

7

Cell and tissue cultures

EBV transformation

Cell culture

Assisting the enlargement and diversity of our

biobank collection

Phase 1- BiobankingProvidesProvides

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)

EquipmentEquipment 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- GenomicsProvides Provides

Wide range of genomic Wide range of genomic technologiestechnologies

Expert help, technical Expert help, technical assistance assistance

SequencingSequencing Fragment analysis Fragment analysis Gene expression Gene expression SNP genotypingSNP genotyping MLPAMLPA DNA Methylation DNA Methylation QQ-PCR-PCR

Equipment Equipment Genetic Analyser

ABI3130xl ABI Prism 7900 HT RT-PCR NanoDrop

spectrophotometer Photodocumentation Standard Lab equipment

Phase 1- Bioinformatics

ProvidesProvides Access to databasesAccess to databases Storage of project dataStorage of project data Specialized softwareSpecialized software Expert help in project designExpert help in project design Data analysis and interpretationData analysis and interpretation

EquipmentEquipment

Intranet with 15Intranet with 15 computer computer workstationsworkstations

File serverFile server Database server for genetic and Database server for genetic and

clnical dataclnical data Application serverApplication server LIMS (Nautilus Thermo Scientific)LIMS (Nautilus Thermo Scientific) FirewallFirewall

Phase 2 -MicroarraysProvides

Gene expression profiling

CGH arrays

SNP detection

Fusion gene microarray

Microarray based DNA- methylation profiling

Analysis of siRNA, miRNAs

Equipment

Hybridization oven with 24 slides capacity

Agilent Laser array scanner with carrousel for 48 slides

Phase 2 - Laser Phase 2 - Laser microdissectionmicrodissection

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 - MetalobolomicsPhase 2 - MetalobolomicsEquipment MMC and NGL

Thermo LC/MS hybrid system

Single quadropole GC/MS with EI ionization

DelfiaExpress fluorescent system

Victor D fluorescent and luminescent system

Two HPLC systems

Provides

Profiling and analysis of biological fluids – plasma, urine of patients aiming at new biomarker detection

Investigation of the molecular events in cells and tissues in cancer and/or apoptosis

Investigation of possible relationships between known genomic disorders and metabolomic profiles

Investigation of nutrition in relation to metabolism in disease and health.

Phase 2 - Cell cultureCell cultureProvides

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 ResourcesHuman Resources

Coordinator 1Management 3Post Docs 2Bioinformatician 1IT Specialist 1Technicians 4Research PhD students 4Clinical PhD students 10

Research GroupsResearch Groups Neurogenetics Neurogenetics Psychiatric and behavioural Psychiatric and behavioural

geneticsgenetics OncogeneticsOncogenetics OphalmogeneticsOphalmogenetics Pharmacogenetics and Pharmacogenetics and

pharmacogenomicspharmacogenomics Population geneticsPopulation genetics Genetics of common complex Genetics of common complex

disorderdisorder

Neurogenetics

Molecular Analysis

• DNA sequencing

• Haplotype analysis

• Linkage

• Expression

• Predisposition

2

DNA Bank Clinical Registry

Hereditary Peripheral

Neuropathies

1

Epilepsy

Dementia

Parkinson

Alzheimer

Achievements

3

• New mutations

• New clinical forms

• New Loci

• New genes

• Improved genetic and clinical diagnostics

• Recommendations for genetics counseling and

diagnostics

Molecular Medicine CenterMolecular Medicine Center

EUROPEAN CMT consortium

Funding:

National Institutes of Health, USAMuscular Dystrophy Association, USA

The Neuropathy Association of the USAFlanders Science Fund, Belgium

National Science Fund, MESScience Fund, MU-Sofia

Department of NeurologyMU-Sofia

Department of PediatricsMU-Sofia

Department of PediatricsMU-Plovdiv

Publiciations since 2005

7 Bulgarian 10 International

European and American Patent

NeurogeneticsNeurogenetics

Department of GeneticsMU-Varna

European network TREAT-NMD

DNA bankClinical and genetic

database

Affective disordersBig families

Sibpairs, TriosCase/controls

Molecular Analysis Achievements

Association studies

•Association studies•Linkage analysis•LD and haplotype analysis

1 2 3

Psychiatric and Behavioural Psychiatric and Behavioural GeneticsGenetics

Association studies

Phenotype and Genotype databaseNew linked lociSusceptibility genes

AddictionsCase/controls

Behavioural geneticsAutism

Sibpairs, triosCase/controls

Phenotype and Genotype database

Phenotype and Genotype database

European Consortium on affective disorders

Funding

Alexander von Humboldt Research Foundation, GermanyAlexander von Humboldt Research Foundation, GermanyBIOMED1, BIOMED2 programs of ECBIOMED1, BIOMED2 programs of EC

NIDA, USANIDA, USANHMRC, Australia

National Science Fund, Ministry of Education and Science

Science Fund, MU-Sofia

Department of PsychiatryMU-Sofia

Local PsychiatristsDepartment of Psychiatry

MU Pleven

Publications

18 international5 Bulgarian

Psychiatric and Behavioural Psychiatric and Behavioural Genetics Genetics

Bulgarian Addictions Institute

Initiative for Health Foundation


OncogeneticsBiobanking

DNA Tumor Plasma

MSIMethylation Sequencing

MLH1/2MLPA

BRAF analysis

Sequencing BRCA1/2 genes

SNP genotyping -

Association studies

Gene Expression

Genetic Counseling

Carrier testing

Targeted therapy

Register of Familial Cancer

Molecular Genetics

Diagnostics and

ProphylacticsHNPCC

FAP

Endometrial Cancer

Breast Cancer

Prostate Cancer

Larynx Cancer

Brain tumors

Financing

Program “Research Capacity” National Science Fund, MES

Science Fund, MU-Sofia

Publications 2005 г

3 Bulgarian4 International

OncogeneticsOncogenetics

МБАЛ “Св. Марина”MU-VArna


IMPACTIMPACT, PRACTICALPRACTICAL, , Prof. R Eeles, Prof. R Eeles,

ICR, Sutton, UK.ICR, Sutton, UK.

FP7, REGPOTFP7, REGPOTProf. J. Lubinski, Prof. J. Lubinski,

Pomeranian Medical University,Pomeranian Medical University, Poland.Poland.

Dr. Markku Vaarala, Dr. Markku Vaarala, Department of Pathology, Department of Pathology, University of Oulu, FinlandUniversity of Oulu, Finland

Department Pathology

Trakia University, St.Zagora

Univ.Hospital “Maichin Dom”

MU-Sofia

Clinical Center GAstroenterology

UH “Tzarica Joanna”MU-Sofia

National Oncological

Institute

Univ. Hospital “Pirogov” MU Sofia

DNA Bank Clinical database

Retinitis Pigmentosa

Molecular Analysis Achievements

Association study

• Linkage analysis• Haplotype analysis• DNA sequencing

1 2 3

Ophtalmogenetics

DNA sequencing

• New mutations• Genotype-Phenotype correlations

Congenital Glaucoma

Age Related Macular Degeneration

AMD

New mutation

Genetic tests

Financing

National Program Genomics National Science FundScience Fund, MU-Sofia

NHMRC, Western Australia

Department of NeurologyMU-Sofia

Publications


OphtalmogeneticsOphtalmogenetics

Foundation Minority Health Problems

Department of OphtalmologyMU-Sofia


Institute of Ophtalmology

London

Financing

National Science Fund, МОНScience Fund, MU-SofiaScience Fund, MU-Pleven

Department

Biochemistry

MU-Sofia

PharmacogeneticsPharmacogenetics

Central Lab of Drug monitoring and clinical

pharmacologyNational Cardiology Hospital


Department Clinical Pharmacology

MU-Sofia

MU-PlevenMU-Plovdiv

University of Lausanne, Switzerland

Publiciations


EducationEducation Courses in molecular medicine for Courses in molecular medicine for

medical studentsmedical students Courses in molecular pathology and Courses in molecular pathology and

genetics for biology studentsgenetics for biology students Specialised training for postgraduate Specialised training for postgraduate

studentsstudents Technological basis and scientific Technological basis and scientific

supervision for MSc and PhD students in supervision for MSc and PhD students in molecular biology and geneticsmolecular biology and genetics

Expert help to researchers Expert help to researchers

SMEs & NGOs

MMC

Molecular Medicine Center

Local Networking

AgroBioInstitute (ABI) Centre of Excellence in Plant Biotechnology

Bulgarian Academy of Sciences

Sofia University,Faculty of Biology

Medical Universitiesin Pleven, Varna, Plovdiv,Stara Zagora

Nutrigenomics Centre MU Varna

Genome Centre for Common Diseases

MU Sofia

International International Networking Networking

Institute of Ophtalmology, London, UK

CMM IHCRCEdinburgh, UK Poland

Life & Brain Centre, Bonn, Germany

Flanders Interuniversity Institute of Biotechnology, Belgium

MMC

Washington University St. Louis, USA

University of Western Australia

Molecular Medicine Center

Microarray Core Facility (MAF), VU University Medical

Centre/ Cancer Centre Amsterdam

Dissemination of knowledgeDissemination of knowledge

MMC web siteMMC web site Journal SubscriptionsJournal Subscriptions Regular SeminarsRegular Seminars Open Door Days Open Door Days National Consultative meeting National Consultative meeting

““Molecular medicine in Bulgaria: Molecular medicine in Bulgaria:

Prospects and Challenges” 2008Prospects and Challenges” 2008 Workshops with mediaWorkshops with media

“ “Ethical aspects of genetic Ethical aspects of genetic research” research”

Research conferencesResearch conferences

MMCMMCSustainability and FinancingSustainability and Financing

6

8

13

International

NSF

SF-MU-Sofia

Projects Projects 20020099 г г6

8

4

Projects Projects 2005 2005 гг

MMCMMC – – Scientific profileScientific profile

0

5

10

15

20

25

2000 2002 2004 2006 2008

MMC&NGL

BIOCHEMISTRY&MMC

Publications of MMC, NGL and the Publications of MMC, NGL and the Department of BiochemistryDepartment of Biochemistry,, MU- Sofia MU- Sofia

Molecular Medicine Center Molecular Medicine Center

key aspectskey 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 Molecular Medicine Center Phase 3Phase 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 3Towards MMC –Phase 3

2008-20102008-2010 National program for Centres of excellence National program for Centres of excellence

““Molecular Medicine Centre (MMC) as a major national research Molecular Medicine Centre (MMC) as a major national research infrastructure in the field of biobanking, functional genomics, proteomics infrastructure in the field of biobanking, functional genomics, proteomics and metabolomics”.,and metabolomics”., PI Prof. V. Mitev, PI Prof. V. Mitev, Project CVP01/0123 (2008-2010), Contract DO02-118/2008Project CVP01/0123 (2008-2010), Contract DO02-118/2008

NSF, Ministry of Education and Science (90%) and MU- Sofia (10%)NSF, Ministry of Education and Science (90%) and MU- Sofia (10%)Total Budget Total Budget 1 534 056 Euro1 534 056 Euroof which for Equipment of which for Equipment 1 187 446 Euro1 187 446 Euro

2010-20152010-2015 Project University Research Complex Project University Research Complex

URC01_03/ 2010-2015 URC01_03/ 2010-2015 PENDING!!!!PENDING!!!!

““University Complex for biomedical and translational research”University Complex for biomedical and translational research”

NSF, Ministry of Education and Science (90%) and MU- Sofia (10%)NSF, Ministry of Education and Science (90%) and MU- Sofia (10%)Total Budget requested: Total Budget requested: ~ 15 000 000 ~ 15 000 000 EuroEuroof which for equipment for the CoE of which for equipment for the CoE 3 306 015 3 306 015 EuroEuro

Create research clustersCreate research clustersMU –Sofia and PlovdivMU –Sofia and Plovdiv

New research coresNew research coresNeuroimaging Core, MU-SofiaNeuroimaging Core, MU-SofiaMicroscopy Core, MU- SofiaMicroscopy Core, MU- SofiaResearch core at Faculty of Pharmacy, MU-SofiaResearch core at Faculty of Pharmacy, MU-SofiaResearch complex for Molecular Biology and Immunology, MU-Research complex for Molecular Biology and Immunology, MU-PlovdivPlovdiv

Upgrade existing cores, especially BioinformaticsUpgrade existing cores, especially Bioinformatics Create national network for biobanking resourcesCreate national network for biobanking resources Upgrade of facilities for fundamental research in Biology, Upgrade of facilities for fundamental research in Biology,

Microbiology, Pharmacology, PhysiologyMicrobiology, Pharmacology, Physiology Enhance capacity for clinical research at University HospitalsEnhance capacity for clinical research at University Hospitals Increase capacity of existing central laboratories for Increase capacity of existing central laboratories for

translational researchtranslational researchNational Genetic LaboratoryNational Genetic LaboratoryClinical ImmunologyClinical ImmunologyCentral Laboratory for Drug Monitoring and Clinical Central Laboratory for Drug Monitoring and Clinical PharmacologyPharmacology

National University Complex for Biomedical and Translational

ResearchMF, MU-Sofia 24 departments

PF, MU-Sofia 5 departments

MF, MU-Plovdiv 3 departments

9 University Hospitals and

2 National Centers

Budget justificationBudget justification Total budget requested Total budget requested ~ 15 000 000 Euro~ 15 000 000 Euro for 4 years for 4 years

projectproject

90 % from NSF, Ministry of Education, Youth and Science90 % from NSF, Ministry of Education, Youth and Science10 % from MU-Sofia and MU-Plovdiv10 % from MU-Sofia and MU-Plovdiv

EquipmentEquipment 69 %69 % ConsumablesConsumables 8 %8 % SoftwareSoftware 1 %1 % Operational costsOperational costs 3 %3 % Human resourcesHuman resources 7 %.7 %. Networking Networking and Trainingand Training 5 %5 % Dissemination Dissemination 1 %1 % Indirect costsIndirect costs 6 %6 % New core facilities renovation and furniture – from the New core facilities renovation and furniture – from the

budget of MU-Sofiabudget of MU-Sofia

National Network

MMC – part of ERAMMC – 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

Documents

ENHANCING THE CAPACITY OF BIOMEDICAL RESEARCH IN BULGARIA Molecular Medicine Center Medical University - Sofia