7.342: Week 11 Questions

Post discussion, questions, or comments about the Week 10 course material here.

Amber

Okada et al

I don't really understand Figure 4C, the Wright-Giemsa staining.

Elizabeth

Georgi

Grignani et al.

So PML and PLZF are fused to RARa and this causes improper repression of key genes involved in hematopoetic differentiation and consequently leukemia by oligomerization and enhanced NCoR/SMRT recruitment. What is the normal function of these proteins? Almost all I find is leukemia related

Holly

Kathy

Okada: Their explanation for why Figure 3E RNAi MLL-AFX showed 0 colonies seems a bit dodgy, since it could also be that the experiment didn't go well? And if their explanation is correct (that a certain level of hDOT1L is required for survival), then their therapeutic goal of curing MLL by inhibiting hDOT1L seems unlikely, since the dose would have to be just right so as not to kill the human as well.

Grigani: What types of drug design approaches could be taken to solve a problem like this--where the target has two very similar domains, but only one of them should be targetted?

Manpreet

Grigani et al:

Fig. 3b - The text says that constructs 6 and 7 demonstrate that the region 2158 - 2239 are required for optimal binding. Construct 11 contains this region, but still has a very low percentage of PZLF bound.

Okada et al: Fig. 2 - I don't understand why they show colocalization with staining instead of showing coimmunoprecipitation (as they do in Fig. 1)

Zak

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