Team:Arizona State/Notebook/May
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{{:Team:Arizona_State/Templates/sidebar|title=Notebook: May}} | {{:Team:Arizona_State/Templates/sidebar|title=Notebook: May}} | ||
+ | __NOTOC__ | ||
+ | == Thursday, May 5 == | ||
+ | * Pitching our CRISPR idea to Xiao | ||
+ | * Needs to be more accessible (how can we explain CRISPR to a non biologist?) | ||
+ | |||
+ | == Wednesday, May 11 == | ||
+ | * Leader sequence- conservation, what activates (link to HN repression paper) | ||
+ | :* We know it is AT rich | ||
+ | :* Can we insert our own promoter? | ||
+ | * How robust is CRISPR? | ||
+ | * We need a proof of concept- GFP silencing | ||
+ | :* Will need 2 plasmids since CRISPR will probably linearize any target | ||
+ | :* Signal intensity correlated with expression | ||
+ | :* "Repress the repressor" | ||
+ | :* As vanilla as possible | ||
+ | * How can we be compatible with the Biobrick standard? | ||
+ | * What happens if we insert our own CRISPR plasmid into a cell with a native system? | ||
+ | |||
+ | == Thursday, May 12 == | ||
+ | * Problems with targeting essential genes- endogenous CRISPR inserts are selected against | ||
+ | :* Any resistance targeting will be heavily selected against | ||
+ | :* Only laboratory applications? | ||
+ | * Modeling ideas: | ||
+ | :* Target vital genes- how does the cell respond? | ||
+ | :* Look at rate of transmission during replication | ||
+ | :* Population dynamics- how is CRISPR array transferred throughout a colony of cells? After a phage challenge? | ||
+ | * What is our end game with CRISPR? Realistically what could it be used for in the real world? | ||
+ | |||
+ | == Monday, May 16 == | ||
+ | * Talking about leader sequence- we should be able to insert our own lac promoter to express the CAS genes and the CRISPR array. | ||
+ | |||
+ | == Tuesday, May 17 == | ||
+ | * Finished semi-official proposal for project | ||
+ | * Some form emails | ||
+ | * How to construct our plasmids: | ||
+ | :* PCR our CAS genes incorporating appropriate restriction sites | ||
+ | :* Get the array synthesized? | ||
+ | |||
+ | == Wednesday, May 18 == | ||
+ | * How many repeat / spacer units? What do we need to take into account when deciding this? | ||
+ | * How can we make our design modular and easily customizable? | ||
+ | * Synthesize an array with 3 repeats and restriction sites at spacer locations? | ||
+ | * Which part of GFP gene do we put in our 32bp spacers? Does it matter? | ||
+ | * Are we targeting DNA or RNA? | ||
+ | :* DNA: CAS, much more literature = we know more about the mechanism = greater chance of success | ||
+ | ::* How do we get GFP to stay in the cell if we target it with CRISPR? Use a separate plasmid, but without antibiotic selection mechanism the cells will die. | ||
+ | ::* "You think of it as a happy GFP story...but really there's a lot of whipping going on. You kill the whole bacterial family until you just get the GFP ones." | ||
+ | :* RNA: RAMP, only a few papers in the literature about this (link?), not in very many organisms | ||
+ | |||
+ | == Friday, May 20 == | ||
+ | * Xiao came in this morning, and today we are joined by Abhinav, a BME undergrad in his lab | ||
+ | * DNA method: we can examine the fluorescence curve (flow cytometry) when we add in the GFP plasmid. | ||
+ | :* If it takes a while to decrease, we can then examine what it looks like when CRISPR is added and have a point of comparison. However, if it attenuates quickly, this isn't really an option for us | ||
+ | * Backups: we need to have more genes to target than just NDM-1 | ||
+ | :* Multiple: target a cluster of genes that code for parts of a characteristic | ||
+ | ::* To inhibit the entire characteristic, we would have to silence A, B, and C (or something like this) | ||
+ | * Other ideas: | ||
+ | :* Motility (csgA) | ||
+ | :* Synechocystis (cyanobacteria that is big at ASU) | ||
+ | :* Biobrick with AND gate (need 1-1) | ||
+ | :* Origin of replication, prevent horizontal gene transfer | ||
== Tuesday, May 31 == | == Tuesday, May 31 == |
Revision as of 06:04, 11 June 2011
Notebook: May
Thursday, May 5
- Pitching our CRISPR idea to Xiao
- Needs to be more accessible (how can we explain CRISPR to a non biologist?)
Wednesday, May 11
- Leader sequence- conservation, what activates (link to HN repression paper)
- We know it is AT rich
- Can we insert our own promoter?
- How robust is CRISPR?
- We need a proof of concept- GFP silencing
- Will need 2 plasmids since CRISPR will probably linearize any target
- Signal intensity correlated with expression
- "Repress the repressor"
- As vanilla as possible
- How can we be compatible with the Biobrick standard?
- What happens if we insert our own CRISPR plasmid into a cell with a native system?
Thursday, May 12
- Problems with targeting essential genes- endogenous CRISPR inserts are selected against
- Any resistance targeting will be heavily selected against
- Only laboratory applications?
- Modeling ideas:
- Target vital genes- how does the cell respond?
- Look at rate of transmission during replication
- Population dynamics- how is CRISPR array transferred throughout a colony of cells? After a phage challenge?
- What is our end game with CRISPR? Realistically what could it be used for in the real world?
Monday, May 16
- Talking about leader sequence- we should be able to insert our own lac promoter to express the CAS genes and the CRISPR array.
Tuesday, May 17
- Finished semi-official proposal for project
- Some form emails
- How to construct our plasmids:
- PCR our CAS genes incorporating appropriate restriction sites
- Get the array synthesized?
Wednesday, May 18
- How many repeat / spacer units? What do we need to take into account when deciding this?
- How can we make our design modular and easily customizable?
- Synthesize an array with 3 repeats and restriction sites at spacer locations?
- Which part of GFP gene do we put in our 32bp spacers? Does it matter?
- Are we targeting DNA or RNA?
- DNA: CAS, much more literature = we know more about the mechanism = greater chance of success
- How do we get GFP to stay in the cell if we target it with CRISPR? Use a separate plasmid, but without antibiotic selection mechanism the cells will die.
- "You think of it as a happy GFP story...but really there's a lot of whipping going on. You kill the whole bacterial family until you just get the GFP ones."
- RNA: RAMP, only a few papers in the literature about this (link?), not in very many organisms
Friday, May 20
- Xiao came in this morning, and today we are joined by Abhinav, a BME undergrad in his lab
- DNA method: we can examine the fluorescence curve (flow cytometry) when we add in the GFP plasmid.
- If it takes a while to decrease, we can then examine what it looks like when CRISPR is added and have a point of comparison. However, if it attenuates quickly, this isn't really an option for us
- Backups: we need to have more genes to target than just NDM-1
- Multiple: target a cluster of genes that code for parts of a characteristic
- To inhibit the entire characteristic, we would have to silence A, B, and C (or something like this)
- Other ideas:
- Motility (csgA)
- Synechocystis (cyanobacteria that is big at ASU)
- Biobrick with AND gate (need 1-1)
- Origin of replication, prevent horizontal gene transfer
Tuesday, May 31
- First official day in the lab
- Received two strains of E. coli from life sciences
- (strain info here)
- 1 strain with no native CRISPR system
- Made 4 plates from this source plate (2 each strain)