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Why bigger is better

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Stockholm, April 8, 2010 , p ,

Prof Mathias Uhlen The Science for Life Laboratory Royal Institute of Technology (KTH) Stockholm, Sweden

Big or small science

Hypothesis-driven research

Often small dedicated research groups Scientist driven Cost-effective C t ff ti

Discovery-driven research

Strategic Infrastructure depend Large funding needs

Outline

1. Omics ­ a new era for biology and medicine 2. Science for Life Laboratory 3. 3 The Human Protein Atlas project 4. From basic to applied research ­ Woodheads g 5. Concluding remarks

Omics ­ a new era in biology and medicine

Systematics in science

18th century ­ biology 19th century ­ chemistry 20th century ­ physics 21st century ­ life science and medicine y

Pyrosequencing Ronaghi, Uhlen & Nyren (1998) Science 281, 363-365.

Source: Nature 464, 670 (2010)

Personalized genomics

Generated with 454 (pyrosequencing)

Omics, biology and disease

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Genomics RNA profiles

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Protein profiles

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Interactomics

Protein "parts list"

Systems biology gy

Pathways, Biomarkers, Drug Targets

High-throughput molecular bioscience

1. Infrastructures for high-throughput biology (i.e. genome sequencing) 2. Large-scale projects (difficult from standard funding agencies) 3. Multi-disciplinary projects (translational medicine) 3 M lti di i li j t (t l ti l di i ) 4. Technology competence (sample handling and data generation) 5. Bioinformatics and systems biology competence

Broad Institute (MIT/Harvard)

· · · · ·

150 MUSD in annually funding (90% project-based) project based) Six technology platforms ­ four focus areas Each program led by a professor 160 associated members (MIT/H i d b (MIT/Harvard faculty) df l ) 800 employees (additional 700 associated) p y ( )

Science for Life Laboratory

Science for Life Laboratory (two sites)

Based on strategic funding in "Molecular Bioscience" (145 MSEK annually from 2012)

Uppsala:

· 30% of the funding for 2010-2014 · Two faculties · Expansion of existing infrastructures

Stockholm:

· 70% of the funding for 2010-2014 · Three universities (three faculties) · New building (moving existing infrastructures)

Science for Life Laboratory (Stockholm)

Vision: To be one of the leading centers in the world for high-throughput bioscience with focus on genome, protein profiling, bioimaging and bioinformatics with ihf i fili bi i i d bi i f i ih relevance for human diseases Organization: Joint ownership of three universities (KI, SU and KTH) with each person in the center employed by one of the three universities. Funding: 105 MSEK annually in strategic funding from the government (VR) and approximately twice that amount from other sources. Location: Karolinska Institute Science Park

Infrastructure for translational medicine

Antibody-based translational medicine

· Set-up four antibody based SciLifeLab facilities for translational research Set up antibody-based · The worlds largest resource of antibodies · Approximately 20,000 antibodies by 2012

Tissue profiles (IHC) human tissues(SciLifeLab Uppsala)

Subcellular profiles (IF) in cell lines (SciLifeLab Sthlm)

Biobank profiles in patient cohorts (SciLifeLab Sthlm)

Tissue profiles in rodent models (SciLifeLab Sthlm)

Next generation plasma profiling

Throughput: 150,000 assays in one run !!!

Population-based biobanks (> 10 000 participants)

Many biobank repositories in Scandinavia (with high quality clinical records) Source: P3G Observatory

Swedish Biobanking and biomolecular resources research infrastructure BBMRI.SE

· · · ·

Centralised and automatic biobanking Funded by 130 million (VR) Start mid 2010 for clinical samples 2010, Location at Karolinska, Huddinge

Storage for all types of clinical samples!

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Collection of disease cohorts

Lung cancer Prostate cancer Colorectal cancer Breast cancer Ovarian cancer Malignant melanoma Pancreatic cancer Stomach cancer Kidney cancer Bladder cancer Minimal cognitive impairment Alzheimer dementia Parkinson Amyotrophic lateral sclerosis Multiple sclerosis Instable angina Cardiac insufficiency Cardiac arythmia Venous tromembolism Aortic aneurysm Osteoporosis

Translational medicine

Diagnosis Treatment Phenotyping of patients Follow up Patient data The Clinics/ h Cli i / Universities Patients Biobanking and biomolecular resources research infrastructure BBMRI.SE Samples incl. tissue

Ex Ex xperim xperim mental mental dat dat ta ta

Clinics/Universities Bioinformatics Results Implementation p

Science for Life Laboratory Genes, proteins, sequences G t i Imaging , Models KTH, UU, STU, KI, KTH UU STU KI

Project policy SciLifeLab

· Service projects ­ "fee for service", a base p p j , package is defined g involving sample preparation, analysis and some basic bioinformatics analysis, project result belongs to external PI, SciLifeLab staff normally not included on scientific manuscripts Collaborative projects ­ SciLifeLab staff involved more than the base package, project results belongs to external PI, SciLifeLab staff normally included on scientific manuscripts, external PI is senior author Internal projects ­ SciLifeLab staff responsible for project, project results belongs to SciLifeLab staff, external researchers normally included on scientific manuscripts, SciLifeLab staff is ll i l d d i tifi i t S iLif L b t ff i senior author

·

·

Science for Life Laboratory

· New resource center for high-throughput bioscience · May 2010. Start of center. Approximately 150 researchers in 2011 · Next generation sequencers (nine instruments 2010, including new Illumina) · Next generation antibody-based biobank profiling (150,000 assays per day) · The worlds highest bioimaging throughput for protein profiling of human cells,, g g g g p p p g

tissues and organs (10 new human proteins profiled every day)

· Worlds largest collection of antibodies to human targets

Gamma-house

Alpha-house Al h h

The Human Protein Atlas project

The Human Protein Atlas program

· Started in 2003 · Multidisciplinary program · Systematic generation and use of antibodies to functionally explore the human proteome · F di for the Wallenberg Foundation (non-profit) Funding f th W ll b F d ti ( fit) and EU

The Human Protein Atlas project team

Uppsala University KTH, Stockholm (main site) Seoul

Shanghai Mumbai

The Mumbai team

Dr. Sanjay Navani

12 certified pathologists All images available through internet Web-based annotation system

The Human P t i Atl project Th H Protein Atlas j t

- Systematic generation and use of antibodies to functionally explore the human proteome

Goal

Validated antibodies toward one protein from every human protein y p coding gene by 2014

Status

·98 % of the human protein coding genes have been initiated

Protein Atlas version 6.0 · Launched: 26 March 2010 · More than 11,274 antibodies targeting the proteins corresponding to 8,489 human genes (42 % of the human genes (42 % of the human proteincoding genes) ·More than 9 million images

Daily output: 10 new human proteins 10,000 images 10 000 i 0,5 Terabyte of data

More than 98% of drugs directed towards proteins

· 20,000 genes coding for human proteins · Summary of all pharma protein targets: <5% · P t i not yet studied (no literature): 40% Proteins t t t di d ( lit t ) · A need for global analysis of human proteins

Nature, July 7, 2007 Human Protein Atlas

Central questions in proteomics

·How many proteins are expressed in a given cell ? ·How many proteins (%) are tissue-specific (i.e. brain) ? Is ·Is an organ built up essentially by tissue specific proteins ?

Previously uncharacterized proteins y p

Proteomics ponders prime time

26 SEPTEMBER 2008 VOL 321 PAGES 1758-1761

A resource for neurobiology

Published on-line: November 2009

Iron homeostasis

Published: October 30, 2009

The Swedish Human protein Atlas project team

From basic to applied research - Woodheads

Tree genomics

The Poplar Genome Program

· Started 1997 as a collaborative effort between researchers from The Swedish University of Agricultural Sciences, Umeå University and The Royal Institute of U i it f A i lt lS i U åU i it d Th R l I tit t f Technology Funded by Knut and Alice Wallenberg Foundation To date over 200 000 EST sequences have been produced 24 000 unique sequences found Two unique DNA-array chips, one based on 4 000 wood zone specific genes, the second based on 13 000 genes from several different tissues Third Thi d generation chip with 24 000 sequences is being used now ti hi ith i b i d

· · · ·

·

A new concept for comersialization of research

University groups

46 members

Woodheads W dh d AB

First right of refusal with a pre-determined fee structure

The Forest Market Place

Sveaskog, Stora Enso, Holmen Skog, Bergvik Skog

The Woodheads members

Forestry

Tomas Lundmark

Stress and seedlings Chemometrics

Christiane Funk Per Gardeström Petter Gustafsson Jan Erik Hällgren Jan Karlsson Leszek Kl L k Kleczkowski k ki Åsa Strand Mattias Hedenström Michael Sjöström

Wood and fibre

Rishikesh Bhalerao Markus Grebe Ewa Mellerowicz Björn Sundberg Hannele Tuominen

Fibre and pulp chemistry

Ulf Edlund Per Persson Staffan Sjöberg Lars Wågberg Lars-Olof Öhman

Biomass

Laszlo Bako Maria Eriksson Vaughan Hurry Pär Ingvarsson Stefan Jansson Thomas Moritz Göran Samuelsson Göran Sandberg

Flowering

Peter Engström Ove Nilsson

Material i M t i l sciences

Lars Berglund Anna Carlmark Malkoch Eva Malmström Mark Rutland

Clonal forestry

Sara von Arnold David Clapham

Enzymology

Harry Brumer y Tuula Teeri Qi Zhou

Genomics technology

Joakim Lundeberg g Peter Nilsson Fredrik Sterky Mathias Uhlén Gunnar Wingsle G Wi l

Nutrition and seedlings

Torgny Näsholm Anita Sellstedt A it S ll t dt

Woodheads and SweTree Technologies

· Represents the world's largest academic consortium of top class top-class researchers in forest biotechnology and chemistry · 46 scientists representing the majority of Nordic research in this area · Access to technology platforms worth more than 15 MUSD

Unique position in functional analysis of tree genes: · Wood and fibre development · Control of flowering in trees · Chemical analysis of wood and fibre · Bioinformatics and multi-variate analysis multi-

Resultat

Before SweTree Technologies, one patent during 20 years in this field

Now SweTree has 90 patents

SweTree have 20 employees and another 20 consultants. consultants

Several products commersialized.

Concluding remarks

Big and small is beautiful

· Balance between small scale (hypothesis-driven) research and infrastructure-driven (discovery) research · A portfolio of different funding strategies p g g · Strategic infrastructure funding necessary to be internationally competitive in certain areas of technology driven research technology-driven · A paradigm shift in biological and medical research (mapping of all building blocks of life)

Thanks for your attention ! y

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