1. AN AUTONOMOUS LINEAR DNA CLOCK Richard J. Crossland

2. Overview  Requirements  Objectives  Two designs  Implementation  Software development cycle  Advantages of a linear DNA clock

3. Design 4: Exonuclease only Mechanism for the linear DNA clock showing how telomere shortening eats away into genes that repress cell death pathways. Upon the destruction of the repressor gene by unrepaired telomere shortening, the cell-death pathway becomes uninhibited to kill the cell.

4. Requirements  A ‘construct that sequentially regulates gene expression after a time delay’.  Allows ordered gene expression.  Level of expression at each step is controllable.  Can alter total time in the program and the relative time of each step.  There is a mechanism to initiate the program.  Consistent program duration.  Can be destroyed after program is complete.

5. The Software Development Cycle

6. Objectives 1.Design and simulate alternative models 2.List and specify the parts for my models 3.Locate parts from the scientific literature 4.List parts that need synthesising 5.Evaluate the best model in terms of:  meeting the requirements  availability of existing parts

7. Design 4: Exonuclease only Mechanism for the linear DNA clock showing how telomere shortening eats away into genes that repress cell death pathways. Upon the destruction of the repressor by unrepaired telomere shortening, the cell-death pathway becomes uninhibited to kill the cell.

8. Design 2: the ER2/gap model An ER2 (exonuclease-resistant secondary structure) gene 1 2 3

9. Implementation in Java

10. Advantages of a linear DNA clock  Timing specified by order and distance, not concentration.  Autonomous to the cell. Not dependent on extracellular signals.  Regulates expression of chromosomal or linear DNA genes  Ethical consideration: ensures the destruction of all GM genes.