Progress in molecular biomedicine
MUDr. Ing. RNDr. Peter Celec, PhD., MPH Institute of Molecular Biomedicine www.imbm.sk
Francis Crick (1916 – 2004) Nobel prize 1962 – Physiology or medicine
3 4 James Watson (1928 – ) Nobel prize 1962 – Physiology or medicine
5 6
7
DNA is information!!!
8 Gene expression regulation
9 Signalling pathways
10 ...but...
11 12
Jak – Janus (Roman god of gates and doors) Kinase Jak – Just Another Kinase STAT – Signal Transducers and Activators of Transcription APS – Adaptor protein with Pleckstrin homology and Src homology 2 domains C-Cbl - Casitas B-lineage Lymphoma EPO – Erythropoietin
13 Frederick Sanger (1918 – ) Nobel prize 1958 – Chemistry 1980 – Chemistry
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John Craig Venter (1946 - ) Genome sequencing
Francis Sellers Collins (1950 - )
18 Microarray
19 GWAS
• No a priori hypothesis • Large numbers of patients • Extremely important selection of patients/controls • High false positive rate • Replication samples • High frequency – low effect size
Pharmacogenetics
Pharmacogenetics
Pharmacogenetics
HT sequencing
• Next generation sequencing • 454, ABI Solid, Illumina • Re-sequencing Personal genomics
Synthetic biology
• Production of synthetic microorganisms • Technology (detoxification, production, therapy?)
Nobel Prize in Physiology or Medicine 2007
"for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells" Mario R. Capecchi Sir Martin J. Evans Oliver Smithies 1/3 of the prize 1/3 of the prize 1/3 of the prize USA United Kingdom USA University of Utah Salt Lake City, UT, USA; Cardiff University University of North Howard Hughes Cardiff, United Carolina at Chapel Hill Medical Institute Kingdom Chapel Hill, NC, USA b. 1937 b. 1925 b. 1941 (in Italy) 37(in United Kingdom) 38
39 Knock-out mice
• Reverse genetics • Function of gene products
• Knock-in mice • Conditional ko mice • Tissue specific ko mice
Gene therapy
RNA interference
• Silencing of genes • Post-transcriptional regulation of gene expression • siRNA, shRNA, miRNA... • Gene function • Pathogenesis • Therapy Nobel Prize in Physiology or Medicine 2006
"for their discovery of RNA interference - gene silencing by double-stranded RNA"
Andrew Z. Fire Craig C. Mello 1/2 of the prize 1/2 of the prize USA USA Stanford University School of University of Massachusetts Medicine Medical School Stanford, CA, USA Worcester, MA, USA b. 1959 b. 1960 44 RNA interference
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Shinya Yamanaka (1962 - ) Stem cells
iPS
• Reprogramming of differentiated cells • Pluripotency • No immune response
• Without retroviral vectors • Without oncogenes The Nobel Prize in Physiology or Medicine 2012