Day 2- Single Cell Modeling

After the coffee break and some illuminating discussions, we came back to the next session: single cell modeling!

Philip Nelson- Single-photon sensitivity in human vision

Philip started this session by giving us a really nice background on the “evolvement” of science. If we have nice night/dim light vision, we would have a better chance of survival-not falling to be a prey! However, there is this notion that the emission of light is lumpy and random, and so is the capture/absorption of light. This leads us to wonder, what is the sensitivity of human vision (perception threshold)?

He goes on to discuss the landmark experiment done by Hecht on determining the minimum number of photons required for perception of light dating back to 1942, and some considerations involved in the experiment’s design. Barlow later pointed out there could be discrepancy due to false positive reports. He also discovered the role of spontaneous isomerization in vision perception. Later on, Baylor’s single cell data showed that there are not only spontaneous isomerizations, but also some lower signal rumble. Barlow also has the insight that ” the very first synapse must discarded some genuine signals”, which Rob Smith claimed later that it is “discarding half of the real signals”.

By using the “high-tech” instruments available now, scientists are able to confirm directly that rod cells impose no threshold, and test out the models proposed. Take home message here is that even with challenging technical details, we could still try to have the model which in Philip’s words: “The best fitting model is the one that maximizes a likelihood function defined by the rather limited experimental dataset.”

 

Po-Yi Ho- Interrogating the Bacterial Cell Cycle by Cell Dimension Perturbations and Stochastic Modeling

Po-Yi is testing the growth law of bacteria by perturbing the cell dimensions and looking at the bacteria cell cycle, using E.coli as a model system.

Single bacteria cells grow exponentially. Particularly, average E. coli cell volume scales exponentially with growth rate, with a scaling exponent equal to the time from initiation of a round of DNA replication to the cell division at which the corresponding sister chromosomes segregate, this is known as the Schaechter’s growth law. So how are cell division and DNA replication coupled and regulated? They found that cells initiate replication at a constant size delta per origin of replication. So they proposed this “adder-per-origin” model, which states that cells add a constant volume delta per origin between initiations, then divide after a constant C+D minutes.

When they try to perturb the bacterial cell dimensions by varying the expression levels of mreB and ftsZ (bacterial homologue of actin and tubulin, respectively), they found that decreased mreB levels resulted in increased cell width (with little change in cell length), whereas decreased ftsZ levels resulted in increased cell length. Moreover, they also found that the growth law remained valid over a range of growth conditions and dimension perturbations, which is kind of impressive! In conclusion, the timing of replication initiation governs that of cell division, and cell volume is the key.

 

Rosanna Smith- Gene reporters and the problem of measurement in live cells

Rosanna showed that even though fluorescence reporters are a convenient tool for us to measure protein expression in live cells, there could be some “side-effects” (that are not so loved obviously) that could perturb the results and affect the interpretation of data.

They showed that some reporters that are used to assess gene expression may have noise that impacts the single cell reporting. As an example, they used the pluripotency factor Nanog, and looked at the stochastic transcription from two alleles. They illustrated that different reporters can have different Nanog expression patterns, meaning that the reporters will perturb the dynamics that we are originally trying to measure.

This talk prompts me to think more about the experimental design and the intrinsic technical difficulties associated!

***

After a delicious and satiating lunch along with nice relaxing small talks, we are ready for the cultural tour to National Palace Museum, and the highly-anticipated Taipei 101 tour! The National Palace Museum has all the art treasures dating back to thousands of years ago! Next, we went up the observatory deck of Taipei 101. The elevator is pretty impressive (even for people afraid of height), it only took us 37 sec to get to floor 89 (382 meters above the ground)! The view of the whole Taipei city is amazing, although there was some fog and the visibility was not the best. The wind damper used to stabilize this skyscraper is also pretty impressive, it helped this tall building survive through different typhoons that hit Taiwan!

-Ivy

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