Cell Identity

• Determined by types and amounts of proteins in the cell

• Protein identities and amounts controlled by gene expression

• Differential gene expression leads to cell differentiation

Differentiation

Divide Differentiate

Stem Cells

DifferentiatingCell

Mature Tissue Cell

Blood Cell Differentiation

Regulating Gene Expression

gene

a

b

c

d

mRNA

protein

Gene Expression Controla) transcription

b) processingc) stabilizationd) translation

Cell Must be Signaled to Change

gene

a

b

c

d

mRNA

protein

Gene ExpressionControl

a) transcriptionb) processingc) stabilizationd) translation

Extracellular Signals

1) Growth factors

2) Hormones

3) Cell-Cell contacts

Types of Signaling

Example-Ras Signal Transduction

Zbigniew Walaszek et al, Cellscience Reviews Vol 1, No 3 2005

Ras Signal Transduction

Malorye AllisonNature Biotechnology 26, 509 - 517 (2008)doi:10.1038/nbt0508-509

Malorye Allison Nature Biotechnology 26, 509 - 517 (2008)doi:10.1038/nbt0508-509

Signal Transduction Complexity

http://upload.wikimedia.org/wikipedia/commons/thumb/2/29/Signal_transduction_v1.png/800px-Signal_transduction_v1.png

Cell Division

Fundamental property of living things

Incredibly complicated processCell must ensure coordination of growth, genome duplication and cell division Must not enter duplication cycle unless

resources are plentiful Must not divide before genome is completely

duplicated

Cell Cycle

Division process takes about 24 hours in humans

Signals and Transduction Drives Cell Cycle

Cell Cycle can be Stopped

Example, Tumor Suppressor p53

DNA damage causesp53 to be activated.

p53 blocks cell cycle

How Does Cancer Happen?

Mutations that incorrectly activate any protein in the Ras pathway can cause loss of cell cycle regulation

EGF, ErbB, Ras, Raf, Mek, Erk, Elk, Srf, Fos

But what about p53?

p53 is also Mutated

Over 50% of human tumors have p53 mutations

Multiple Events Required for Cancer

Alterations in the pathway of colon cancer are well known

cropwiki.irri.org/.../2/23/Bioinformatics2.jpg

Bioinformatics Contributes to our Understanding