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[Challenge Topic] Tuning cell cycle

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Posted at 2012-5-3 20:21:02 | All floors |Read mode
我有个不成熟的想法...能不能做出这样一个design 让yeast能够自己evolve出不同的cell cycle length(本来想说age的...做起来不太现实),或者可以设计一个circuit能够像一个调节音量大小的按钮来调节cell cycle progression,想让它快一点就变快了,想让它慢一点就变慢了...大概这样的一个想法,能做为team challenge的topic么~~
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Posted at 2012-5-3 20:29:22 | All floors
That sounds interesting. It can be a good topic if more details are developed.  
I'm interested in what kind of oscillation, in a non-linear dynamic sense, can have its frequency easily tuned?
And why do you think it is important to let yeast cycle by its own pace, expect for that it is really fun?
给我一块二向箔,清理用

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 Author| Posted at 2012-5-3 21:23:17 | All floors
Reply zhiyuanli Add Thread


   What I wanna ask is how the cell cycle length is evolved. If applied in other condition, will the cell cycle length be changed?So if we could be able to  pace the cell cycle, we would be able to gain some insight into what aspect contribute to the evolution of cell cycle length...
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IP  122.198.133.233

Posted at 2012-5-3 21:51:52 | All floors
Cell cycle length is tunable by many kinds of input, like nutrient condition, osmotic stress, DNA damage, microtubule drug and so on. There is a science paper "Robust, Tunable Biological
Oscillations from Interlinked Positive and Negative Feedback Loops" by Jim Ferrell and Chao Tang discussing how to tune the amplitude and frequency of an oscillator. It's in nonlinear dynamics view. In biology view, speaking of cell cycle, I believe in most cases, the period is prolonged at checkpoints.

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Posted at 2012-5-4 16:48:54 | All floors
Reply xili.liu Add Thread


    Thought cell cycle may work in nonlinear ways, but the the trend caused by a condition change is monotonous in most cases. So the cycle is tunable even when prolonged from checkpoints, perhaps not a linear way.

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IP  162.105.160.10

Posted at 2012-5-5 01:12:48 | All floors
这个挺有意思的,我的想法是能不能做一个counter,让细胞能够数自己的分裂代数,然后通过调节这个counter来调节细胞的死亡时间。我感觉让yeast延长寿命还是挺困难的,但是缩短寿命的话不一定那么难,只要到一个时间死掉就行(这个时间需要小于等于正常的life span)~
做出来的话其实挺有意义的,比如可以利用这个思路治疗癌症什么的。因为现在大部分的抗癌药都是直接来杀死癌细胞的,对健康细胞会有影响。如果用这个方法的话,其实不用做到癌细胞特异性那么严格,只要组织特异性就好(考虑到不同组织的细胞的life span可能不同)。
求拍砖!

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Posted at 2012-5-5 21:27:08 | All floors
Reply QX_Cai Add Thread


   抱一个先~这个我喜欢。其实multicellular里面这个counter被认为是telomere端粒。至于yeast以及其它,好像就是各种损伤由于没能及时得到修复而累积下来,比如DNA damage,坏掉的蛋白、细胞器等等,最后就死掉了,不知是否有个专门的counter,要能做一个那很好玩~
在肿瘤细胞里有端粒缩短的情况,因为telomere维持genome的稳定,短了就容易出现末端融合,尤其在p53活性缺乏时容易癌变。但是多数肿瘤细胞中是存在端粒酶(延长telomere)活性的,这也是它们长生不死的一个原因,所以已有实验抑制telomerase来治疗肿瘤,据说结果不错。这东西貌似比较火~
所以,正常细胞里transient表达telomerase应该可以治疗衰老相关疾病,但是如果已经癌变了,可以通过抑制telomerase治疗。
我了解的大致这样,欢迎Pia
王紫薇

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 Author| Posted at 2012-5-5 22:55:37 | All floors
Reply QX_Cai Add Thread如果只是做一个cell cycle counter的话~别人早就做过啦~建议搜Biocomputing: A Yeast Cell Cycle Counter


   
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 Author| Posted at 2012-5-5 22:57:25 | All floors
Reply Amber.Zw.W Add Thread


   yeast里面不完全是这样 就是tel1 mutant (telomere长度一直不变)它和 WT lifespan一样长
不过以上已经走题很远了...
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 Author| Posted at 2012-5-5 22:59:48 | All floors
Reply QX_Cai Add Thread


   如果要用“定时炸弹”治疗肿瘤...一是要怎么把定时炸弹弄到特定的癌变细胞里(这肯定不是小分子...至少是一个circuit)二是反正是要杀肿瘤细胞,干嘛还要定时...不管活几代统统杀死就好了呀~
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IP  162.105.160.201

Posted at 2012-5-5 23:31:33 | All floors
Reply Zairan Add Thread
固然能够直接杀死癌细胞是最好的,但关键是抗癌药物的副作用是非常大的,因为不能做到癌细胞特异性,正常的细胞都被杀死一大坨。定时炸弹可能能从某种程度上限制细胞的生长,副作用可能没那么强。不过确实这个circuit的deliver是个问题,现在很多研究的抑癌方法都存在这个技术障碍,就是用什么载体比较安全。我记得去年有个nature的文章也是用合成了一个circuit来抑制癌细胞的,且是癌细胞特异性,对正常细胞影响不大。我们只能说这是一种治疗癌症的思路,但是真正用于临床还有非常远的路。
至于cell cycle的counter,不知道前人做的是啥,用什么细胞系做的,我来研究研究

   

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Posted at 2012-5-5 23:39:22 | All floors
Reply Zairan Add Thread
确实扯的很远了。。。zairan可以把主题再扯回来。。。

   

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IP  162.105.160.109

Posted at 2012-5-11 21:11:20 | All floors
Does it have anything to do with the mechanism of circadian rhythm in organisms like Arabidopsis or mammals?

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Posted at 2012-5-13 23:02:37 | All floors
Reply QX_Cai Add Thread


    咦,这个和我之前的一个想法很像~~是因为当时看到了一篇science文章,讲的是counter, "Synthetic Gene Networks That Count"

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Posted at 2012-5-13 23:03:55 | All floors
Reply Zairan Add Thread


    谁能告诉我用什么分岔做这种time tuning 比较合适 @caoys

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IP  162.105.21.109

Posted at 2012-5-14 13:32:39 | All floors
Reply ShaoBin Add Thread


    Hopf分岔就行了,也能调的,就是响应不够明显,不过要是能稳定的调节频率,Hopf分岔还是最好的吧
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