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Fundamentals of Molecular Biology
Malay BhattacharyyaSRF, MIU, ISI Kolkata
July 29, 20101 ISS, MIU, ISI Kolkata
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Outline of the presentation
IntroductionGeneCentral dogma of molecular biologyProteinMicroRNA
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Introduction
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Organism
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Eukaryote-prokaryote
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Phylogeny of organisms
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Body
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Cell
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Nucleous
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Chromosome
July 29, 201010 ISS, MIU, ISI Kolkata
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DNA
July 29, 201011 ISS, MIU, ISI Kolkata
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Sequence data
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Nucleotides & sugar phosphate backbone
July 29, 201013 ISS, MIU, ISI Kolkata
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Open problems
Aligning multiple DNA/RNA/Protein sequences (multiple sequence alignment is an NP-hard problem)Finding the conserved sequences for drug design (closest substring finding is an NP-complete problem)Sequence analysis of short length RNAs (length margin)
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Gene
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Gene
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Microarray profiling
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Snapshot of expression data
Gene ID c1 c2 c3 c4 n1 n2 n3 n4 n5 n6
G1 … 1.2 1.6 1.8 1.1 1 2 1.3 4 2 1.1
G2 … 1.1 1.5 1.3 1.8 2.1 1.1 1.1 1.1 2.3 1.5
G3 … 1.2 1.7 1.8 1.1 2 1.1 2.1 0.8 1.1 1.9
… … … … … … … … … … … …
G100 … 2.1 1.6 1.7 1.4 2.3 2.7 2.8 2.9 1.3 2.1
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Gene ID t1 t2 t3 t4 t5 t6 t7
G1 … 1.2 1.9 2.4 3.2 1.1 5.7 7.4
G2 … 3.2 3.9 4.4 5.3 3 7.8 9.5
G3 … 1 2.1 3.2 6.2 7.3 8.5 3.7
… … … … … … … … …
G1000 … 2.2 3.1 6.3 5.3 8.2 2.5 4.3
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Open problems
Study on intronic regions (lack of data)Methylation pattern analysis of genes (scarcity of large-scale data)Proper framework for co-expression, contra-expression, differential co-expression, co-expression dynamics (lack of mathematical analysis)
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Central dogma of molecular biology
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Gene→RNA→protein
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Transcription
July 29, 201022 ISS, MIU, ISI Kolkata
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Translation
July 29, 201023 ISS, MIU, ISI Kolkata
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Promoter
July 29, 201024 ISS, MIU, ISI Kolkata
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Types of promoters
Core promoterRNA polymerase binding site (within 1 kb from the upstream)
Transcription start site- Pol I transcribes genes encoding rRNA- Pol II transcribes genes encoding mRNA, miRNA, etc.- Pol III transcribes genes encoding tRNA, short RNAs, etc.
Proximal promoterTranscription factor binding site (within 2-3 kb from the upstream)
Distal promoterSpecific transcription factor binding site (within 10kb from the upstream)
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Gene ontology
Level n
…
Level 4
Level 3
Level 2
Level 1 GO
Biological Process
locomotion growth
Molecular Function
catalytic
Cellular Component
Organelle
Intra organelle
Inter organelle
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Is a
Part of
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p-value
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E
Ne n
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Open problems
Transcription termination protocol (lack of information)Quantifying the biological significance of a gene cluster (proper mathematical framework is lacking)
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Protein
July 29, 201029 ISS, MIU, ISI Kolkata
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Types of proteins
StructuralKeratin, Actin, Fibrillin, etc.
FunctionalCiliary neurotrophic factor, Erythropoietin, etc.
EnzymesOxidoreductases, Transferases, Hydrolases, etc.
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Protein
July 29, 201031 ISS, MIU, ISI Kolkata
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Protein structure
July 29, 201032 ISS, MIU, ISI Kolkata
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Open problems
Drug design (the only approach is hypothetical analysis)Host-viral protein interaction network analysis for diseases (lack of data for many diseases)
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MicroRNA
July 29, 201034 ISS, MIU, ISI Kolkata
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RNA tree
July 29, 201035 ISS, MIU, ISI Kolkata
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Biogenesis of miRNAs
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Regulation
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Open problems
Regulation of miRNAs by transcription factors (lack of proper information fusion)The transcriptional protocol for different categories of miRNAs (scarcity of data)
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References
1. J. Setubal and J. Meidanis, Introduction to Computational Molecular Biology,PWS publishing company, Boston, 1999.
2. M. S. Waterman, Introduction to Computational Biology: Maps, Sequences andGenomes, Chapman & Hall, London, 1995.
3. B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts and P. Walter,MolecularBiology of the Cell, Fourth Edition,Taylor & Francis Group, 2002.
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Thank you
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