Twinkle Medicine Hunter Of Cancer

1. Twinkle Medicine Hunter Of Cancer LZU-China iGEM Team 2013

2. Content 3 1 Human Practice Experimental 2 Results & Discussion 4 Introduction

3. Chap.1Chap.2Chap.3Chap.4 Background: About Cancer Estimated Number of Persons Alive in the U.S. Diagnosed with Cancer in 2006 (N = 11.4 M survivors) Estimated Number of Persons Alive in the U.S. Diagnosed with Canceron January 1, 2006 by Time From Diagnosis and Gender(Invasive/1st Primary Cases Only, N = 11.4 M survivors Estimated Number of Female Cancer Survivors in the U.S. in 2006 (N = 6.2 M survivors)

4. Chap.1Chap.2Chap.3Chap.4 Background: About Cancer What cause cancer? Cancer cells come from normal cells, what changed? Gene mutation

5. Chap.1Chap.2Chap.3Chap.4 Background: Overview of NF-κB classical signaling pathway Activated NFkB were found in almost 70% cancer cells. NFkB signaling pathway has become a variety of malignant tumor therapy and drug discovery is an important target.

6. Chap.1Chap.2Chap.3Chap.4 Background: Overview of NF-κB classical signaling pathway TNF-α IL-1 IL-1R TNFR Cytoplasm TRADD MyD88 RIP IRAK FADD TRAFs NF-κBSignaling Pathway PMA TAK1 TRAF6 MEKKS PKC IKKs P P Ub IκB-α IκB-α NF-κB p65/50 P Proteasome Nucleu IκB-α cIAP1/2 Bcl-xL/2 Survivin ICAM-1 Cyclin-D1 VEGF Gene expression P NF-κB p65/50

7. Chap.1Chap.2Chap.3Chap.4 Background: Negative feedback loop of NF-κB Negative feedback loop

8. Chap.1Chap.2Chap.3Chap.4 Background: Goal How to Change the situation • Traditional : • LOW accuracy • Mice live short/ Can’t take long-term detection ?

9. Chap.1Chap.2Chap.3Chap.4 Experimental: Device Promoter: 4 copies of κB Binding sequence IκB+GFPTerminator Pref Suff pSB1C3

10. Chap.1Chap.2Chap.3Chap.4 Experimental: Design Cancer Why IκBα exists? NF-κB signaling pathway feedback loop dynamis To last a long term detection Sacrifice less mice

11. Chap.1Chap.2Chap.3Chap.4 Experimental: Device Promoter: 4 copies of κB Binding sequence IκB+GFPTerminator Pref Suff pSB1C3

12. Chap.1Chap.2Chap.3Chap.4 Background: Goal Fluorescent light Fluorescent light Time Time Oscillation represents drug’s duration time. NF-κB signal is inhibited.

13. Chap.1Chap.2Chap.3Chap.4 Results & Discussion: Results Experimental: DU-145 IκBα GAPDH shRNA- IκBα - +

14. Chap.1Chap.2Chap.3Chap.4 Results & Discussion: Results Experimental: DU-145 IκBα GAPDH DU145 Cell

15. Chap.1Chap.2Chap.3Chap.4 Results & Discussion: Future Goals Experimental: 1. Improve specifity:building the fine-adjusted in other cells. 2. Shorten twinkle cycle-time: show some features in pharmacokinetics of drugs. 3. Achieve semiquantitative measure: detect the light intensity of GFP and make a standard curve. 1. Making our drug screening system work better.

16. Chap.1Chap.2Chap.3Chap.4 Results & Discussion: Application Experimental: 1. How to do: inject DU-145 in which have a moderate expression level of IκB. 2. Long-term drug evaluation system: tumor grow slowly, mice survive longer. 3. Sensitive system: observe twinkle instead o measuring the size of tumor. 1. Making our drug screening system work better.

17. Chap.1Chap.2Chap.3Chap.4 Human Practice Experimental: Our team had a interchange with Peking iGEM team and BIT iGEM team in August. We shared our own idea to each other, and offered advice for the problem. Our Team’s member Li Xiaomenghad been honoured to visit the BIT iGEM 2013 Team’s lab. And help them to characterize and construct a part of Cr sensor.

18. Chap.1Chap.2Chap.3Chap.4 Results & Discus Human Practice Experimental: We held two promotion meetings concerning iGEM for all students in our school and Lanzhou No.1 Meddle School successfully. Meanwhile, the opening day of iGEM lab has been excellently work out with the amazing enthusiasm in this summer vacation.

19. Chap.1Chap.2Chap.3Chap.4 Acknowledgements Ph.DJinbo Yang, HuyuanFeng & Their Labs Institute of Cancer Biology and Drug Screening of Lanzhou University School of Life Science of Lanzhou University

20. THANKS!