8.591J | Fall 2014 | Graduate, Undergraduate

Systems Biology

Pre-class Reading Questions

The Pre-Class Readings Questions are meant to facilitate interactions during class between students.

LEC # QUESTIONS
2

What type of signals alter the activity of transcription factors within a cell?

How is it possible that some proteins are able to drastically change their concentrations in minutes in response to certain stimuli?

How does the modular nature of the genome give plasticity to transcriptional networks?

Why is it easier to alter transcription networks by mutating gene regulatory regions vs. genes themselves?

3

What is a network motif?

In the study of response time in negative autoregulation we learned that the degradation term a[X] can be ignored at early times. Explain why this term can be ignored?

For a negatively autoregulated gene, why does the repression term K vary much less from cell to cell compared to gene expression levels?

4

Transitions between bistable states are usually reversible. Give two possible reasons for why differentiation in Xenopus oocytes is irreversible.

Using the genes and techniques from Figure 3, describe how you might add memory to an OR logic gate.

How does the gene expression variation scale with the following quantities? Transcription rate, translation rate, mRNA half-life.

5

What controls do the authors use to make sure that oscillation are not just an artifact of GFP expression?

What parameter determines the period of oscillations in simple networks supporting limit cycles? Could it be “tweaked”?

The authors show that oscillations are not tied to cell doubling. However, do cells need to be actively dividing for the repressilator to oscillate?

6

How are out-degree distributions different from in-degree distributions in transcriptional networks?

How does the mean number of type 10 subgraphs (figure 4.1 (b), Uri Alon) scale with N if the mean connectivity is kept constant?

In “Emergence of Scaling in Random Networks,” why do Barabasi and Albert claim that growth is necessary for creating scale-free networks?

7

What does Uri Alon assume about the signals Sx and Sy? Why do these assumptions need to be made?

Using Figure 4.9 (in Uri Alon), estimate the delay for the arabinose FFL. Explain your answer from a biological standpoint.

For large values of the repression factor F, how does doubling F affect the response time of an I1-FFL?

8

Why do the authors choose to image a membrane protein instead of a cytoplasmic protein? Of the membrane proteins, why do they choose tsr?

How do the authors take advantage of photobleaching in their experimental design?

How do the authors show that single mRNA molecules are responsible for gene expression bursts?

9

What are the possible mechanisms leading to transcriptional bursts in eukaryotes?

What is the potential benefit of a stochastic switching mechanism over an environment sensing mechanism in a fluctuating environment?

Which genes in eukaryotes tend to be noisy / not noisy and why?

10

What is f(n) and g(n) for simple negative autoregulation? Assume cooperativity to be 1.

When might you want to use the Fokker-Plank formalism vs the master equation formalism?

In the Fokker-Plank equation, is n a continuous or a discrete variable?

11

Why is reciprocal motion an unlikely way for micron-sized microorganism to swim?

How efficient is E. Coli’s method of locomotion? How does the efficiency of the system relate to E. Coli’s metabolic needs?

What is the minimum distance that E. Coli must move in order to sample a new environment?

12

Why is it important for bacteria chemotaxis to display perfect adaptation?

How does the amount of post-translational modifications per Che receptor alter the dynamic range of nutrient sensing?

In chapter 7, the authors discusses robust and fine-tuned model of chemotaxis. What advantages does each model confer?

13

Of the six potential stable states of a reaction-diffusion system with two interacting molecules, which stable state does not yet have a concrete biological example?

Gierer and Meinhardt showed that “a short-range positive feedback with a long-range negative feedback” is the basic requirement for Turing pattern formation. In the context of an activator-inhibitor system, what does this requirement mean in terms of the diffusion coefficients of the activator and the inhibitor?

Why is the model with nonlinear degradation rate considered a more robust mechanism for developmental patterning?

14 [Not Available]
15

Why are most changes in protein sequence those that substitute an amino acid with another of similar properties?

How does population size determine the fixation of a given allele?

In a neutral site, what is the rate of substitution per generation equal to? How does this change for advantageous or deleterious mutations?

16

In an equivalent model of mutational incorporation how does the distribution of successful mutations depend on the initial distribution of available mutations?

Beginning at equal concentrations, how does the ratio of the populations Ny and Nc evolve in the case where beneficial mutations are rare? How do they evolve if the mutation rate is high?

What function did the authors use to model the distribution of beneficial mutations?

17

How do D. Weinreich et al. define fitness of bacteria?

How do the authors define accessible evolutionary paths?

Which of the 5 mutations discussed in the artcile has the highest mean proportional increase in fitness? What does this mutation do?

18

Consider frequency-dependent selection (figure 4.2 in the book). What is the condition on the stability of the internal fixed point if the first derivatives of Fa and Fb are equal at this point?

If the internal fixed point is stable, will it be a Nash equilibrium of the game?

In the Rock-Paper-Scissors game, what are the possible outcomes if we wait long enough?

19

What advantages does asymmetrical anticipatory regulation have over symmetrical?

How do the authors make sure that the genes upregulated in anticipation of oxidative stress are not involved in the response to heat shock?

What factors can make stochastic phenotype switching more advantageous than responsive switching?

What is the optimal switching rate in their simple stochastic model?

20

(Nowak) It is mentioned that vaccination reduces the basic reproductive ratio. The basic reproductive ratio depends on 4 model parameters. Which of these parameters will be affected by vaccination?

(Nowak) Why is superinfection not advantageous to the parasite population as whole? (Optional question)

(Moran) When and why might outcrossing be favorable, or unfavorable?

21

Describe the stages in the evolutionary cycle of the multi-clone model. What is the source of the increased phase lag?

Is predator evolution necessary for phase delays, and why?

The idea of predator-prey interactions was originally formulated by Volterra to explain the observation that during wartime, when fishing activities were reduced, the relative abundance of predatory fish increased. Please explain his arguments.

For sustained predator-prey oscillations, we define the phase lag as the time between the peak in prey abundance and the peak in predator abundance. What is the typical phase lag?

22

What is a catastrophic bifurcation?

Explain the early-warning signals in time series that are proposed in the paper.

What are the spatial patterns that can arise before a critical transition?

23

In a stepping-stone model, how do beneficial mutations spread through the populations? How is it different from the well-mixed model?

Briefly, what are the possible explanations for the unusually low levels of genetic diversity in the populations?

How does the spatial scale of interaction affect dynamics in an RPS community?

24

How are metacommunity and local community defined?

In a metacommunity, what is the most likely number of individuals within a given species?

In a local community, why is there a peak in the histogram of the number of individuals within a species?

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