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Twinkle Medicine Hunter Of Cancer

LZU-China iGEM Team 2013

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Content

12

34Introductio

n

Experimental

HumanPractice

Results & Discussion

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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 Female Cancer Survivors in the U.S. in 2006 (N = 6.2 M survivors)

Chap.1 Chap.2 Chap.3 Chap.4

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

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Background: About Cancer

Chap.1 Chap.2 Chap.3 Chap.4

What cause cancer?Cancer cells come from normal cells, what changed?

Gene mutation

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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.

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Background: Overview of NF-κB classical signaling pathway

NF-κB Signaling Pathway

FADD

IκB-αNF-κB

p65/50

NF-κBp65/50

IκB-αcIAP1/2Bcl-xL/2SurvivinICAM-1Cyclin-D1VEGF

Gene expression

Cytoplasm

PKC

Nucleu

IKKs

PMA

TNF-α IL-1TNFR IL-1R

MEKKS

TRADD

RIPTRAFs

TRAF6TAK1

MyD88

IRAK

P

P

P

IκB-αUb P

Proteasome

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Background: Negative feedback loop of NF-κB

Chap.1 Chap.2 Chap.3 Chap.4

Negative feedback loop

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Background: Goal

How to

Changethe situation

Chap.1 Chap.2 Chap.3 Chap.4

Traditional : LOW accuracy Mice live short/

Can’t take long-term detection

?

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Experimental: Device

Promoter:4 copies of κB

Binding sequence

Chap.1 Chap.2 Chap.3 Chap.4

IκB+GFP Terminator

Pref

Suff

pSB1C3

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Experimental: Design Cancer Why IκBα exists?

Chap.1 Chap.2 Chap.3 Chap.4

NF-κB signaling pathway feedback loop dynamis

To last a long term detection Sacrifice less mice

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Experimental: Device

Promoter:4 copies of κB

Binding sequence

Chap.1 Chap.2 Chap.3 Chap.4

IκB+GFP Terminator

Pref

Suff

pSB1C3

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Background: Goal

Chap.1 Chap.2 Chap.3 Chap.4

NF-κB signal is inhibited.

Oscillation represents drug’s duration time.

Fluo

resc

ent l

ight

Fluo

resc

ent l

ight

Time Time

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Experimental: Results & Discussion: Results

Chap.1 Chap.2 Chap.3 Chap.4

DU-145

IκBα

GAPDH

shRNA- IκBα - +

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Experimental: Results & Discussion: Results

Chap.1 Chap.2 Chap.3 Chap.4

DU145 Cell

DU-145

IκBα

GAPDH

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Experimental: Results & Discussion: Future Goals

1. Making our drug screening system work better.

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.

Chap.1 Chap.2 Chap.3 Chap.4

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Experimental: Results & Discussion: Application

1. Making our drug screening system work better.

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.

Chap.1 Chap.2 Chap.3 Chap.4

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Experimental:

Chap.1 Chap.2 Chap.3 Chap.4

Human Practice

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 Xiaomeng had been honoured to visit the BIT iGEM 2013 Team’s lab. And help them to characterize and construct a part of Cr sensor.

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Experimental: Results & Discus

Chap.1 Chap.2 Chap.3 Chap.4

Human PracticeWe 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.

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Ph.D Jinbo Yang, Huyuan Feng & Their Labs

Institute of Cancer Biology and Drug Screening

of Lanzhou University

School of Life Science of Lanzhou University

Chap.1 Chap.2 Chap.3 Chap.4

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THANKS!