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[Challenge Topic] exclusive size control mechanism

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Posted at 2012-5-3 21:11:24 | All floors |Read mode
I have a workshop topic. It's about exclusive size control mechanism. I list several related question here:

In single cell level, how does a cell measure its own size? What's the possible mechanism? What's the limit for a cell's size? Can we have a happily growing yeast cell with size as big as a grape? What's the minimal requirements to reach size  homeostasis? There can be many different ways to reach size homeostasis, each generates different shape of distribution. Is there any best mechanism? Or different mechanism is  adapted to different environment? Unicellular organism always modular size with nutrient environment, is there any universal correlation between energy state and cell size?

In organ level, how does an organ measure its own size? What's the possible mechanism? When an organ grows, there are two possible ways, one is the volume of each cell increases, the other is the number of cell increases. Both ways exist in real system. How does the macroscopic size feeds back to cell size and cell number? Organ size must be adapted to individual size during growth. Some organs grow with body growth, some don't change much. For example, from infant to adult people, heart volume increases several folds, while brain volume doesn't increase as much. How is that achieved?

In individual level, iIn warm blood animals, there is a plateau for individual growth. After a fast growing period, there is a very long period of time that growth stops. While in at least many kinds of cool blood animals, like fish, snake, lizard, turtle..., the plateau is less significant. Growth is almost through the whole life. What's the mechanism underlining this phenomenon? Is our metabolic system limiting our growth? What did our ancestor pay to maintain body temperature? And what's the effect of sexual selection on population size?

And so on.

Anyone interested are welcome to discuss. We can make it more formulated and doable. Have fun!

Xili

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Posted at 2012-5-3 21:52:58 | All floors
Can we have a happily growing yeast cell with size as big as a grape? ...
xili.liu replied at 2012-5-3 21:11
I love the idea of a grape-size yeast. It should be tasty

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Posted at 2012-5-3 22:06:28 | All floors
I like this topic.
during a team challenge, we should introduce some background knowledge,  and maybe at least half of this workshop is about the theory part. In all current theoretical models of size control, which one do you like? How about tyson's model?
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 Author| Posted at 2012-5-4 12:05:31 | All floors
Tyson's model is beautiful, but very misleading. The assumption that cyclin is proportional to cell size is too strong. I'm thinking about what about we lose the constraint, forget about all the molecular basis, just think about it conceptually, that what are the minimal requirements to control cell size and keep population homeostasis.  For background knowledge, I prefer "Cell growth and size homeostasis in proliferating animal cells" by Marc Kirschner, and several very old papers by Hartwell like "Unequal division in Saccharomyces cerevisiae and its implications for the control of cell division" and some old works in E coli. What to you think?

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Posted at 2012-5-4 12:45:03 | All floors
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I‘m wondering... Why size control is so important? Let's forgot about the knockout phenotype, just image a cell that can divide whenever it wants... what's the evolutionary disadvantage? Can we set a fitness function about that , and do an in-silico evolution  to seek for the best size-control mechanism?
   
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 Author| Posted at 2012-5-4 13:22:21 | All floors
At least there are several constraints. As the cell is growing bigger, the surface/volume ratio gets smaller, the nutrient uptaking efficiency gets lower and cell growth slows down. And there should be an optimized nucleus/cytoplasma ratio or genome/cell size ratio, which is determined by diffusion rate and other factors. But what is interesting is normal cell size is far below those limits. E coli cells growing in good environment for 25 years gain bigger size than wild type. Fat cell must have disadvantages when response to stress and bad environment. There is no surprise that cell compromises  growth to division. The really interesting question is how to balance those two behaviors, how much time or energy to spend on growth and how much to spend on division. An in-silico evolution or simulation will be very helpful.

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Posted at 2012-5-4 14:27:42 | All floors
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So if I understand correctly, there is at least one  trade-off in cell size control: on one hand, cell shouldn't wait too long to divide or else it will be too big to get nutrient; on the other hand, if it divide too frequently to keep a small size, it is energy consuming.... so it sounds more like a "growth speed" control and "size control" is only the consequence?

   
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 Author| Posted at 2012-5-4 15:20:00 | All floors
It's quite possible in unicellular organism. I also feel size is only a consequence in budding yeast. Then how to explain "size control" in mammalian cell?

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Posted at 2012-5-4 16:41:43 | All floors
How can a single cell "feel" or "measure" its size? Or size control is a group level selecting, that the individuals with the best size will grow better?

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Posted at 2012-5-4 16:48:03 | All floors
Reply yscao Add Thread
Good question. Wallace Marshall in UCSF should love this topic -- without microscope and glass, how can cell "know" how long/tall/fat itself is?

I remember that for fission yeast, there are some signal molecules mainly locate in two sides of the cell. The concentrations decays with distance within the cell, so once the concentration in cell center drops below a threshold, the cell know it is long enough for division. Don't know how about budding yeast.  -> it also means we can pull the fission yeast by mechanical force and see whether it is forced to divide~
   

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Posted at 2012-5-4 16:53:51 | All floors
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    It's Pom1, that help fisson to feel its length with a concentration degree. This molecular machanism can work because fission grow just along an axis. Budding grows as a ball, perhaps another molecular can form a concentration degree?

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Posted at 2012-5-4 17:06:03 | All floors
Just as mentioned in the second paragraph, how can a multi-cell individual "measure" its cell number? Or this information has just coded in the genome, which indicates that from an embryo to a mature individual, stem cells can only differentiate for limited times, and afer that, homeostasis between cell death and product is built.

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Posted at 2012-5-4 18:15:15 | All floors
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    It's Pom1, that help fisson to feel its length with a concentration degree. This molecu ...
yscao replied at 2012-5-4 16:53

Xili, is there any known stuff that "measure" budding yeast's size?  what will happen if you inject a yeast with a lot of cytoplasm from another yeast?

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Posted at 2012-5-4 18:49:33 | All floors
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    explosion, I think

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 Author| Posted at 2012-5-4 19:15:46 | All floors
Reply yscao Add Thread
Second this, hehe.


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Posted at 2012-5-5 20:12:47 | All floors
Reply root Add Thread


Interesting. but to pull the cell with some force is a little too complicated in manipulation and might become a stress, the cell might be forced to response in other ways instead of deviding, im afraid.
Why not just lower the concentration of those signal molecules by a inducible promotor?
and what kind of molecules and the paper about this, thanks~
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Posted at 2012-5-5 20:22:25 | All floors
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    what do u mean by "differentiate for limited times"?

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I guess he meant the differentiation process is limited. After several times of differentiation, cells get mature and can't differentiate any more.  Posted at 2012-5-5 21:37
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Posted at 2012-5-5 21:02:55 | All floors
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It's quite true  external mechanical force is difficult to reach and control. How about making cell expand passively by extending the  length and dense of cytoskeleton by overexpression skeleton protein?   Will it be less harmful?

   

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Posted at 2012-5-5 21:49:28 | All floors
yep! it seems to be much more comfortable for the cell to grow with more "bone" than pulled(为什么说pull让我突然想起五马分尸了呢)
truly it produces tall and huge individuals in mammals to accelerate long bone growth (see Yao Ming~^0^).
but the synthesizing of cytoskeleton is a process or, just a "part", or "result"of growth. i mean, it grows, so it synthesizes cytoskeleton, instead of the opposite. if overexpressed, the cell might become harder? or stronger?or sick of this burden, for it takes up too much material and machine for protein synthesis?
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 Author| Posted at 2012-5-5 21:53:47 | All floors
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I'm not sure about whether did I get your question. But referring to "fat cell", by shutting off cln3, one can simply get a very fat round cell 100 times bigger than wild type. I didn't try, but if waiting longer, the cell volume could be even bigger. And, I didn't see much growth defect on those cells.
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