Chemical Biology of the Genome

I. An integrative approach to chemical biology
a) Philosophy behind the integrative approach
b) Ensembles of molecules possess fundamentally different properties than individual molecules
c) Physical tools for studying ensembles and their properties
d) Chemical Genetics: A powerful approach to study cellular functions
e) Genes and Genomes: An integral entity

II. Genes, Genomes and Genome Dynamics
a) Genes: The building block
Definition, identification, functional genes: an evolution in thoughts and ideas
b) Genome: Complexity and Diversity. The organization of genes, the organization of genomes, the structure of chromatin
c) Unstable genes: Biology and Chemistry. Unstable loci, why some genes are unstable (chemical and physical perspectives). Biological trigger for jumping genes
d) The Dynamic Epigenome: Epigenetic Modifications and reversible changes. Reversible histone modifications, DNA methylation, Hydroxymethylation, Noncoding RNA and genome stability

III. Chemical modifications of the genome
a) Electrophilic and Nucleophilic substitution reactions
b) DNA structure
c) Chemical modifications of DNA
d) Chemical modifications of proteins
e) Enzymes involved in chemical modifications of proteins and DNA
f) Modification of histones and their role in gene regulation

IV. DNA sequence recognition by proteins and gene regulation
a) DNA recognition motifs of DNA-binding proteins
b) Sequence recognition versus shape recognition
c) Thermodynamics of sequence-specific recognition
d) Origin of sequence specificity, in prokaryotes and eukaryotes
e) Regulation of gene expression in prokaryotes: Chemical Principles
f) Regulation of gene expression in eukaryotes: Chemical Principles
g) Designed Transcription factors
h) Gene regulatory networks

V. Elucidation of genome sequence and functional architecture by chemical biology approach
a) Genome Sequencing: rapid evolution in the technology
b) Genome-wide Cooperation: GWAS and EpiGWAS:
c) GWAS: Regulatory elements, Transcription and replication perspective, enhancer, super-enhancer, RNA pol II binding sites
d) EpiGWAS: methylome, histone modifications, book marking
e) 3D architecture of the Genome: chromatin territories, CT and ICT relations (dynamics), small molecule metabolites interactions, functional foci, movements of territories
f) Capturing the genome dynamics: capturing dynamic genome (3C to 5C) implications in disease diagnosis and prediction

VI. Chemical genomics: Understanding differentiation and disease (Using siRNA and small molecule)
a) Intervention in gene networks using SiRNA/ShRNA, miRNA and anti-miR
b) Small molecule modulation of iPS
c) Elucidation of Neural and Muscle differentiation pathways by means of chemical biology approach
d) Elucidation of Disease Biology
e) Drug resistance pathways

VII. Chemical Biology: Drug discovery targeting the functional genome
a) Using networks perspectives to discover drug targets
b) Altered DNA methylation as drug targets: DNMT inhibitor, DNMT inhibitor and metastasis, correlations with histone modifications
c) Combinatorial therapeutic molecules targeting in the reverse direction
d) Targeting specific gene expression to counter Drug resistance:
e) Anti-miR as therapeutics
f) Nanodelivery of drugs: a targeted Phenomenon. Classes of drug delivery vehicle
g) Applications: receptor ligand modification and nano-vehicle, organ specific delivery, indirect targeting, tissue toxicity