A. Factual Knowledge

The first piece of factual knowledge I’ve learned the past few weeks is that X-inactivation differs in different species! I didn’t know that in mice, the paternal X gets reactivated only in embryo-proper cells, whereas in humans it gets reactivated everywhere. This was in comparison to Kangaroos who don’t reactivate it anywhere.

The second piece of factual knowledge I’ve learned is that there are multiple ways to inactive chromatin. I don’t have a huge genetics background, so I didn’t realize histone methylation, histone acetylation, and DNA methylation were all different things. I learned this from reading the midterm 2 paper, in which histone methylation can inactivate certain genes; acetylation can remove histones from that DNA; and DNA methylation tends to inactivate portions of the genome.

 

B. Conceptual Knowledge

I realized that there are many ways for chromatin to become ‘inactive’ and X-inactivation seems to use a different mechanism than normal imprinting! Imprinting is generally quoted as using DNA methylation to silence genes, and that these methylation patterns can be passed on parentally. However, X-inactivation seems to use histone modifications to establish parental source! I thought it was super interesting and found the reason for this that was proposed by the MT2 paper was really confusing.

 

C. Metacognitive knowledge

1. First, I read the paper as best as I could. I allowed myself to get confused. But, it allowed me to form a mental map of all the points the paper was trying to make. Next, I re-read it using google to clarify any questions I had. This allowed me to really understand the arguments they were making and fully comprehend what they were trying to say. Finally, I reviewed each figure without the accompanying text. I tested my understanding of the paper by being able to interpret the figures, and try to deduce what the authors were trying to say by just looking at their data.

2. The hardest part about this particular paper was its length. They made so many points and arguments that after a while, it got confusing to follow. Keeping track of PE vs IVF or 4-cell vs Morula vs Blastocyst was confusing enough, but reading 8 different arguments about them was even harder!

3. When I’m reading papers, I always feel most confident about interpreting what the authors have to say about their results. I enjoy reading about their ‘hypothesis’ or thoughts on strange results they got, and so I feel that I am confident in critically thinking about their proposed explaination or discussion. This was facilitated by me reading the paper several times and really scrutinizing the figures without the text. I think it gave me the opportunity to really look at the data alone, and then compare my own conclusions with the authors’.

Learning Journal- Week 8

	Three things that stood out	Type of knowledge	What makes these things stand out for you	Evidence/how you would test someone on this (select one “thing” only!)
1	Homeotic genes are genes that have the potential to mutate such that a segment develops/adopts the identity of a different segment	Conceptual	I found these fascinating! I didn’t previously know what a homeotic gene was, so to learn about the crazy world of hox clusters was really neat. I like thinking about all the pieces of our bodies that are classified under ‘homeotic’ genes, and it is strange to think about how much we take for granted its complicated regulation.	To test if someone knew what a homeotic gene is, I would likely ask them to identify whether a gene was homeotic based on a description of their WT and mutant phenotypes. For example, one should know a homeotic gene is a gene that can either be gain-of-function to look like the ‘next’ sequential segment, or loss-of-function to look like the ‘previous’ sequential segment. When given a WT phenotype, one should be able to compare a mutant and conceptually understand the patterns associated with mutations in homeotic genes. An example of this would be to look at a segment of your spine and realize that in the WT, each segment is different (T1,T2,T3, T4 etc) but in a mutant, one segment might look like its neighbor instead of itself (T1,T2,T2,T4 etc).
2	Another thing I’ve learned is how imprinting works. I learned that imprinting involves the ‘marking’ of a chromosome based on what sex the parent is. That is, the mother will produce eggs that have maternal imprinting and a father will produce sperm that have paternal imprinting. These maternally and paternally imprinted chromosomes will be passed on to their progeny. The tricky part is understanding how imprinting gets reset in the next generation. The progeny (let’s call it F1) will have one set of maternally imprinted chromosomes and one set of paternally imprinted chromosomes. When F1 creates gametes, the imprinting will be reset, such that if F1 is a female, she will produce eggs with the maternal imprint. These eggs will have the maternal imprint even if the chromosome it has was originally from the father in F0. The same is true for sperm but reverse—it will have a paternal imprint on its one set of chromosomes regardless of whether the chromosome was originally from the F0 father or mother.	Conceptual	I think a better question would be what person WOULDN’T find imprinting interesting. I hadn’t heard about imprinting before either, so to think that my genetics are not just based on what genes I inherited, but also who I got them from is really neat. I was reading an article the other day about how children tend to resemble their father more than their mother, regardless of which gender they were, and I found this interesting. Particularly so because most friends I have get along better to their fathers—and I wonder if there is some kind of evolutionary benefit to this.	I think the best way to test for this knowledge would be to have someone track imprinted genes throughout a phylogeny. Below this table I have drawn out a phylogeny showing the inheritance and imprinting trends of 2 genes. I know I have learned imprinting is because I am able to draw phylogenies like this and apply them to phenotypes in an individual. For instance, in the tree drawn below, I can identify the differential phenotypes in the F2 generations, and how both F2 females and F2 males who inherited chromosome2 from their mothers will gain the maternally imprinted C2, even though it was paternally imprinted in F1.
3	One of the things I feel I am starting to get a real handle on is how to create and describe a full model when given data. An example of this was shown in the midterm, but we do this every week with different problems. What I have learned (or rather, improved upon) is incorporating ALL the data given to me. I have learned how to be thorough in explaining how all data fits my model, and I have also learned what I need to include in order for the model to be complete.	Skills	Interpreting data from developmental-themed papers has always been a challenge for me, since most of my practical skills in paper-reading are actually in ecology (my thesis will be in microbial ecology). I think this course so far has helped me improve my skills as a developmental scientist by changing the way I look at data. In ecology, I find that data tends to emphasize trends, whereas developmental data stresses the importance of noting all details. (Of course, there are some exceptions to this, but in my experience this is what I’ve felt.) Thus, it was challenging for me to switch my perspective from an ecological to developmental and become comfortable (and confident) enough to begin forming models in my head.	I think the best way to test this skill would be to simply show a set of data and allow students to come up with models that incorporate all the information they can gather from it. To emphasize the idea that it is more important to create an ‘accurate’ model than a ‘correct’ one, I would probably also make the data fake– to encourage students to look at the problem without interference of previous knowledge about the system. (If I recall correctly, question 2 on the midterm was like this, and I really enjoyed that!).

 

Chromosome 1= C1                                                  Cx^m=maternally imprinted

Chromosome 2= C2                                                  Cx^p= paternally imprinted

Any other chromosome= Cx

 

 

 

F0.Female (C1, Cx)                F1.Female (C1^m,C2^p)

|Cross——->

F0.Male (C2, Cx)                    F1.male (C1^m,C2^p)

 

 

F1.Female (C1^m,C2^p)                         F2.Female (C1^m,Cx^p)

|Cross———->                                  F2.Female (C2^m,Cx^p)

F1.Male (Cx^m,Cx^p)                             F2.Male (C1^m,Cx^p)

.                                                            F2.Male (C2^m,Cx^p)

 

 

F1.Male (C1^m,C2^p)                             F2.Female (C1^p,Cx^m)

|Cross———->                                  F2.Female (C2^p,Cx^m)

F1.Female (Cx^m,Cx^p)                         F2.Male (C1^p,Cx^m)

.                                                            F2.Male (C2^p,Cx^m)

 

 

 

1. Factual Knowledge

What I learned so far in BIOL 463 are the four major kinds of cis-regulatory elements found in eukaryotic genes. They are promoters, enhancers, silencers, and boundary elements/insulators.

I know I have learned this because I can draw a basic diagram describing their function. I understand that promoters appear right before the transcription start site, and are necessary for transcription to occur. Enhancers, on the other hand, are not necessarily needed and can be located distally or proximally from the gene of interest. Their function is to increase the rate of transcription. Conversely, silencers are DNA elements that decrease the rate of transcription—although, some would argue enhancers and silencers are sometimes interchangeable depending on the cell type/ state of the cell. Finally, I learned that boundary elements/insulators act as ‘shields’ to protect a segment of DNA from the effects of other cis-regulatory elements or chromosome-packing proteins.

2. Conceptual knowledge

The past week, I learned how dorsal affects the formation of the D-V system in Drosophila. I learned that a loss-of-function mutation in the dorsal gene will cause ‘dorsalization’ because no gastrulation will occur, whereas a gain-of-function mutation in the dorsal gene will cause ‘ventralization’ wherein there is gastrulation everywhere.

I know I have learned this because I can explain the mechanism of function by which dorsal mutations cause dorsalization.  The gene dorsal encodes for a protein called Dorsal, which is present in the cytoplasm of all embryo cells, but has the ability to enter the nuclei of only ventral cells. The Pipe-Toll-Spaetzle pathway phosphorylates the protein Dorsal and allows it to break apart from Cactus so it can enter the nucleus of ventral cells only. In the nucleus, it acts as a transcription factor and promotes the transcription of genes necessary for VENTRAL development—that is, for gastrulation. That is why when there is not enough Dorsal on the ventral side (loss of function), no gastrulation occurs and dorsalization results. In contrast, if there was a gain-of-function mutation and Dorsal was found in the nuclei of too many cells, it would result in gastrulation everywhere—also known as ventralization.

3. Skills

One of the skills have I learned so far in BIOL 463 is how to interpret Drosophila development data and make correct statements about what the data means. Previously, I was unsure about how far I could interpret the data and what limitations the data might have, but now I feel confident that I could describe, interpret, and make conclusions about pictures of Drosophila embryos .

I know I have acquired this skill because I have learned from my mistakes on my quiz. On the quiz, I was unsure how I should interpret the different time frames and different distributions of light/dark. I now know to interpret data in its ENTIRETY, including the different time frames (which I had not done previously) and to not get caught up on what I think the data ‘should’ look like. I was trying to over-interpret the data on my quiz, and now I have realized what it means to make conclusions only on the data provided. Hopefully, my evidence for me learning this skill will be evident on the midterm!

4.  What is Factual Knowledge useful for?

I think factual knowledge is useful for being able to describe things, events, or concepts in a succinct and effective way. Terminology, for example, is factual knowledge that is incredibly useful for describing events without having to explain every piece of the event. With terminology, I am able to tell tell you that “the Dorsal protein causes gastrulation when it enters the nuclei of ventral cells because it acts as a transcription factor for proteins involved in gastrulation” without having to also explain what ‘protein’, ‘gastrulation’, ‘ventral’, or ‘transcription factor’ means. Thus, while factual knowledge does not allow people to make inferences or interpret data, it does allow them to describe it.

A. Factual Knowledge

This week, I learned the definitions of  totipotent and pleuripotent. Totipotent refers to the cells formed shortly after fertilization that have the ability to specialize into any kind of cell. It has the most potency of any cell type. Pleuripotent, on the other hand, are the cells that result when totipotent cells first begin to differentiate. Pleuripotent cells can give rise to many different cell types, but is more differentiated than totipotent cells.

I know I have acquired this factual knowledge because I am able to compare and contrast totipotent and pleuripotent cell types (as done above) and also because I am able to apply their definitions to a real-world example. For instance, when C. elegans eggs become fertilized, the resulting zygote is totipotent. Once it divides into 2 cells, the cells are no longer totipotent because they can only grow into their respective ‘sides’ of the worm. In contrast, a human embryo can contain multiple cells but still have identical totipotency in all the cells– which is why an embryo in early developmental stages can split to form two whole individuals rather than two halves of a single person. It is only later in development that the cells become pleuripotent, at which point removal of certain cells may result in physical deformations in the mature fetus.

B. Conceptual knowledge

This week I learned what kinds of information we can obtain from the three broad types of experimental approaches: Look/stain and look, remove something, and add something. From “look” approaches, we can acquire lots of different information such as the location of structure, the appearance of structure, the location or distribution of proteins, the expression pattern of mRNA, the movement of different molecules, and much more. When something is removed. we learn what functions that unit is necessary for. This is in contrast to when you add something, in which case we learn what functions that unit might be sufficient for.

I have acquired this information because I am able to use this conceptual knowledge when analyzing data or exercising my ‘skills’. For example, if you were to present me with a case study in which the deletion of gene Y results in X phenotype, I could tell you that gene Y is necessary for the wild-type phenotype X. Likewise, I would be able to say that in an experiment where you add component A to result in affect B, component A is sufficient to induce affect B.

C. Skills

One skill I have acquired this week is the ability to know how to interpret experimental data– specifically, what data might mean and what limitations certain results have. As an extension of this skill, I also have learned how to identify how one might clarify or resolve the limitations of a particular experiment.

Some examples that I have to demonstrate this ability is:

• Be able to look at the relationships between cell potency and time/stage after fertilization, when transplanting genetic material into egg cells. In this case, it is important to realize that while we can conclude that as time increases potency decreases, we do NOT know that DNA is necessarily being deactivated. It may be that DNA is gradually being discarded as cells become more differentiated. In order to determine whether it is DNA being inactivated, or `DNA being discarded (or something else entirely), DNA could be quantified or sequenced to compare the DNA content between cell stages.
• Be able to conclude the phenotypic effects of the loss of the Rspo2 gene in frogs. Although the results show asymmetrical facial and limb development, it would be best to say that Rspo2 is involved in general facial and lib development, rather than say “it results in the right leg and left face being deformed”. This is because the asymmetrical deformations may be due in part to environmental effects, and that the asymmetry might be partially stochastic (random) regarding which side it effects.