Algorithms in Nature
(brief) introduction to biology
Organism, Organ, Cell
Organism
Types of Cells
Eukaryots:
- Plants, animals, humans
- DNA resides in the nucleus
- Contain also other compartments
Prokaryots:
- Bacteria
- Do not contain compartments
Cell signaling
Cells communication is based on chemical
signals & receptors
If you have the correct receptor, respond to
signal; no receptor = no response
Single-celled organisms receive cues about the
environment, status of other individuals
Process termed the signal transduction
pathway
From signal interacting with receptor to cellular
response
Types of Signals
Local signaling: short-distance
affect the cells that produce them
affect nearby cells (diffuse)
Hormonal signaling: long-distance
Typically found in multicellular organisms &
use circulatory system for distribution
Cell Signaling Stages
1. Reception: signal molecule interacts
with receptor
2. Transduction typically several steps that
involve changes to responder molecules
and downstream targets
3. Outcome: often triggers a cellular
response (effect)
Introduction to Molecular Biology
Genomes
Genes
Regulation
mRNAs
Proteins
Systems
Central dogma
DNA
CCTGAGCCAACTATTGATGAA
transcription
mRNA
CCUGAGCCAACUAUUGAUGAA
translation
Protein
PEPTIDE
Genome
A genome is an organisms complete set of DNA
(including its genes).
However, in humans less than 3% of the genome
actually encodes for genes.
while a much larger % of the genome is transcribed
(miRNAs, lincRNAs, )
A part of the rest of the genome serves as a control
regions (though thats also a small part).
Comparison of Different Organisms
Genome size
Num. of genes
E. coli
.05*108
4,200
Yeast
.15*108
6,000
Worm
1*108
18,400
Fly
1.8*108
13,600
Human
30*108
25,000
Plant
1.3*108
25,000
Biological data is rapidly
accumulating
Transcription factors
DNA
transcription
RNA
translation
Proteins
Next generation sequencing
Genes
What is a gene?
Promoter
Protein coding sequence
Genomic DNA
Terminator
Example of a Gene: Gal4 DNA
ATGAAGCTACTGTCTTCTATCGAACAAGCATGCGATATTTGCCGACTTAAAAAGCTCAAG
TGCTCCAAAGAAAAACCGAAGTGCGCCAAGTGTCTGAAGAACAACTGGGAGTGTCGCTAC
TCTCCCAAAACCAAAAGGTCTCCGCTGACTAGGGCACATCTGACAGAAGTGGAATCAAGG
CTAGAAAGACTGGAACAGCTATTTCTACTGATTTTTCCTCGAGAAGACCTTGACATGATT
TTGAAAATGGATTCTTTACAGGATATAAAAGCATTGTTAACAGGATTATTTGTACAAGAT
AATGTGAATAAAGATGCCGTCACAGATAGATTGGCTTCAGTGGAGACTGATATGCCTCTA
ACATTGAGACAGCATAGAATAAGTGCGACATCATCATCGGAAGAGAGTAGTAACAAAGGT
CAAAGACAGTTGACTGTATCGATTGACTCGGCAGCTCATCATGATAACTCCACAATTCCG
TTGGATTTTATGCCCAGGGATGCTCTTCATGGATTTGATTGGTCTGAAGAGGATGACATG
TCGGATGGCTTGCCCTTCCTGAAAACGGACCCCAACAATAATGGGTTCTTTGGCGACGGT
TCTCTCTTATGTATTCTTCGATCTATTGGCTTTAAACCGGAAAATTACACGAACTCTAAC
GTTAACAGGCTCCCGACCATGATTACGGATAGATACACGTTGGCTTCTAGATCCACAACA
TCCCGTTTACTTCAAAGTTATCTCAATAATTTTCACCCCTACTGCCCTATCGTGCACTCA
CCGACGCTAATGATGTTGTATAATAACCAGATTGAAATCGCGTCGAAGGATCAATGGCAA
ATCCTTTTTAACTGCATATTAGCCATTGGAGCCTGGTGTATAGAGGGGGAATCTACTGAT
ATAGATGTTTTTTACTATCAAAATGCTAAATCTCATTTGACGAGCAAGGTCTTCGAGTCA
Genes Encode for Proteins
Example of a Gene: Gal4 AA
MKLLSSIEQACDICRLKKLKCSKEKPKCAKCLKNNWECRYSPKTKRSPLTRAHLTEVESR
LERLEQLFLLIFPREDLDMILKMDSLQDIKALLTGLFVQDNVNKDAVTDRLASVETDMPL
TLRQHRISATSSSEESSNKGQRQLTVSIDSAAHHDNSTIPLDFMPRDALHGFDWSEEDDM
SDGLPFLKTDPNNNGFFGDGSLLCILRSIGFKPENYTNSNVNRLPTMITDRYTLASRSTT
SRLLQSYLNNFHPYCPIVHSPTLMMLYNNQIEIASKDQWQILFNCILAIGAWCIEGESTD
IDVFYYQNAKSHLTSKVFESGSIILVTALHLLSRYTQWRQKTNTSYNFHSFSIRMAISLG
LNRDLPSSFSDSSILEQRRRIWWSVYSWEIQLSLLYGRSIQLSQNTISFPSSVDDVQRTT
TGPTIYHGIIETARLLQVFTKIYELDKTVTAEKSPICAKKCLMICNEIEEVSRQAPKFLQ
MDISTTALTNLLKEHPWLSFTRFELKWKQLSLIIYVLRDFFTNFTQKKSQLEQDQNDHQS
YEVKRCSIMLSDAAQRTVMSVSSYMDNHNVTPYFAWNCSYYLFNAVLVPIKTLLSNSKSN
AENNETAQLLQQINTVLMLLKKLATFKIQTCEKYIQVLEEVCAPFLLSQCAIPLPHISYN
NSNGSAIKNIVGSATIAQYPTLPEENVNNISVKYVSPGSVGPSPVPLKSGASFSDLVKLL
SNRPPSRNSPVTIPRSTPSHRSVTPFLGQQQQLQSLVPLTPSALFGGANFNQSGNIADSS
Structure of Genes in Mammalian
Cells
Within coding DNA genes there can be un-translated
regions (Introns)
Exons are segments of DNA that contain the genes
information coding for a protein
Need to cut Introns out of RNA and splice together
Exons before protein can be made
Alternative splicing increases the potential number of
different proteins, allowing the generation of millions of
proteins from a small number of genes.
Comparative genomics
Regulatory Regions
Promoter
The promoter is the place where RNA
polymerase binds to start transcription. This is
what determines which strand is the coding
strand.
DNA Binding Motifs
In order to recruit the transcriptional machinery, a
transcription factor (TF) needs to bind the DNA in front of
the gene.
TFs bind in to short segments which are known as DNA
binding motifs.
Usually consists 6 8 letters, and in many cases these
letters generate palindromes.
Example of Motifs
Messenger RNAs (mRNAs)
RNA
Four major types (one recently discovered regulatory
RNA).
mRNA messenger RNA
tRNA Transfer RNA
rRNA ribosomal RNA
RNAi, microRNA RNA interference
Messenger RNA
Basically, an intermediate product
Transcribed from the genome and translated into protein
Number of copies correlates well with number of proteins
for the gene.
Unlike DNA, the amount of messenger RNA (as well as
the number of proteins) differs between different cell types
and under different conditions.
Complementary base-pairing
mRNA is transcribed from the DNA
mRNA (like DNA, but unlike proteins) binds to its complement
mRNA
Transcription
apparatus
TFIIH
RNAPII
Gene
Activators
mRNA
label
hybridization
AUGC
UACG
Perturbation
In many cases we would like to perturb the systems to
study the impacts of individual components (genes).
This can be done in the sequence level by removing
(knocking out) the gene of interest.
Not always possible:
- higher organisms
- genes that are required during development but not
later
- genes that are required in certain cell types but not in
others
Proteins
From RNA to proteins: The
Ribosome
Decoding machine.
Input: mRNA, output: protein
Built from a large number of proteins and a number
of RNAs.
Several ribosomes can work on one mRNA
The Ribosome
Proteins
Proteins are polypeptide chains of amino acids.
Four levels of structure:
- Primary Structure: The sequence of the protein
- Secondary structure: Local structure in regions of the
chain
- Tertiary Structure: Three dimensional structure
- Quaternary Structure: multiple subunits
Secondary Structure: Alpha Helix
Protein Structure
Protein Interaction
In order to fulfill their function, proteins interact with
other proteins in a number of ways including:
Regulation
Pathways, for example A -> B -> C
Post translational modifications
Forming protein complexes
Putting it all together: Systems
biology
High throughput data
We now have many sources of data, each providing a
different view on the activity in the cell
- Sequence (genes)
- DNA motifs
- Gene expression
- Protein interactions
- Image data
- Protein-DNA interaction
- Etc.
High throughput data
We now have many sources of data, each providing a
different view on the activity in the cell
- Sequence (genes)
- DNA motifs
to expression
combine these different data types together to
-How
Gene
a unified
view of the activity in the cell is one of the
-obtain
Protein
interactions
major challenges of systems biology
- Image data
- Protein-DNA interaction
- Etc.