Dylan Paoletti

Dylan Paoletti

Apr 23, 2024

Group 6 Copy 850
1

Steps

The phase 1 project can be broken down into these steps:

  1. Order DNA from IDT (approx 10.6kb)

  2. Phosphorylate and ligate blunt ends (use NEB SDM kit)

  3. Transformation DH5 alpha cells, plate on LB + 100 ug/mL ampicillin

  4. Pick AmpR colonies and miniprep, screen colonies using a restriction enzyme that cuts 2 - 5 times to create diagnostic fragments

  5. Choose 2-3 clones for sequencing using Oxford Nanopore Technology (ONT)

  6. Maxiprep using kit to produce ultrapure plasmid

  7. Begin culturing HEKa (Primary Epidermal Keratinocytes) 

  8. Transform HEKa with plasmids using Lipofectamine DNA Transfection Reagent

  9. Determine transfection efficiency with fluorescence microscopy for presence of EGFP 1 - 4 days after transfection

a) Control plasmid/HEKa

b) GC plasmid/HEKa

10. Optimize lipofection efficiency

11.  (Optional) Prepare complementary DNA (cDNA) and perform Reverse Transcriptase PCR (RT-PCR)

a) Run qPCR on MDM2, EGFP and reference gene

12. Prepare whole cell protein lysates

a) run SDS-PAGE transfer PAGE to nitrocellulose filter, 

b) add horseradish peroxidase (HRP) conjugated mouse anti-human MDM2, EGFP and reference protein TBD

13. Start cancer cell line A431 culture (and possibly another cancer line TBD)

14. Transform HEKa and A431 (and other cancer line) with plasmids using Lipofectamine DNA Transfection Reagent

a) Control plasmid/HEKa

b) GC plasmid/HEKa

c) Control plasmid/A431

d) GC plasmid/A431

e) Control plasmid/another cancer line TBD

f) GC plasmid/another cancer line TBD

15. Determine transfection efficiency with fluorescence microscopy for presence of EGFP 1 - 4 days after transfection

16. (Optional) Prepare cDNA and perform Reverse Transcriptase PCR (RT-PCR)

a) Run qPCR on MDM2, EGFP and reference gene

17. Prepare whole cell protein lysates

a) run SDS-PAGE transfer PAGE to nitrocellulose filter, 

b) add horseradish peroxidase (HRP) conjugated mouse anti-human MDM2, EGFP and reference protein TBD

18. TUNEL assay

19. Run Gel on healthy and cancer cell lines to look for evidence of apoptosis

1 comment

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  • Peter Evans
    Peter EvansResearcher
    This is a working draft, we plan to build out these ideas in the coming weeks. Our goal is to collect data that will assure us that the GC plasmid is functional and expresses proteins from the genes encoded on both operons (MDM2 and Complex-9). We will modify the plasmid slightly, replacing the CMV promoter for the EGFP with an Internal Ribosome Entry Site (IRES). This will make EGFP expression and cellular fluorescence in transfected cells depend on the same promoter as Complex-9. We will also replace the CMV promoter for MDM2 with the EF1a (Human eukaryotic translation elongation factor 1 α1) promoter because CMV has variable strength in different cell lines. Interested in your comments and ideas!
    May 08, 2024

About This Project

Cancer remains one of the most challenging health issues worldwide. Current therapies like chemotherapy, radiation, and surgery often come with significant side effects (off-target effects) and limited effectiveness. To address these limitations, my project proposes leveraging synthetic genetic pathways for cancer therapy. This project capitalizes on the processes involved in DNA damage response to create a targeted and low-cytotoxicity approach to combat cancer.

More Lab Notes From This Project

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