A. Three main things in BIOL463

Please describe, briefly, the three things that you learned in BIOL463 and that you consider to be the “most important” ones.

     One of the things that I learned in this course and that really stuck with me is X chromosome inactivation and the mechanism behind it. Every time there’s a question that requires to me to think up a mechanism involving silencing, I think non-coding RNA-mediated silencing and specifically Xist inactivating a X chromosome.

            It’s also interesting for me to have learned all the mechanisms behind chromatin remodelling. It’s pretty cool to know that there are regions of the chromosome which are considered transcriptionally active or inert, and they can be identified by epigenetic marks which are commonly associated with activation or inertness. What’s even more interesting is how cells will change their epigenetic profile the further they go down their differentiation pathway.

            Genomic imprinting is something I had a lot of difficulty with in this course but I think it’s one of the most important things we learned in the course. The example with Air RNA and how it silences paternal Slc22a3 particularly stuck with me. Genomic imprinting is so complex and can regulate development in a lot of cases and we probably haven’t even scratched the surface of understanding it yet.

 B. Identify types of knowledge

For each of your three “things”, please try to identify what type of knowledge it represents (Factual, Conceptual, Procedural/Skills, Metacognitive).

Xist-mediated X chromosome inactivation and Air RNA silencing Slc22a3 is factual knowledge since there is evidence and research to support these facts. Chromatin remodelling is more conceptual because it deals with theories and models than the other two topics I mentioned. There isn’t anything specific about chromatin remodelling that struck me other than just the general concept, which is why I would classify it as conceptual knowledge.

 C.  What makes “things” stand out for you

For each of your three “things”, please indicate what made it stand out for you.

  I think all of these three topics stood out to me for the same reason: they are examples for why science is so captivating. It’s amazing to think that the three topics I mentioned have so much impact on human development when they seem like just inconsequential concepts on their own. Development is so fickle and my mind is blown every time I try to think about the fine-tuned regulation and just how much regulation is required so we can develop into who we are now. There is so much complexity and we haven’t even come close to describing all of it. I think that’s one of the reasons why it’s so intriguing for me: these concepts make me realize that I know very little and there’s still a lot to discover so I will never be short of questions. There’s a lot of knowledge waiting for me and I just have to go out there and ask testable questions. This is why topics like the ones I mentioned stand out for me.  

 D.  Relevance/use

Please describe, briefly, what you expect each of these three “things” to be useful or relevant for.

   I don’t know if this is an applicable analogy but I always think of scientific breakthroughs as comparable water droplets falling onto stone. After years and years, water will eventually break through the stone and erode it. Breakthroughs are similar: you have to keep going and pushing until finally you make that breakthrough. But science is also unique because discoveries are often made because a scientist somewhere makes a tiny, seemingly inconsequential discovery but that can often be the catalyst for something much bigger later on. Discoveries in science are founded by the work of many people together. The topics I mentioned are small steps for greater discoveries down the road and that’s why they are so relevant.

E.  Three main things in your undergraduate education

Please describe, briefly, the three things that you learned during your undergraduate education and that you consider to be the “most important” ones. Why do you find them so important?

I have learned that I basically know very little of what there is to know in this world. In high school that might’ve scared me but my undergrad education taught me that this is something to be embraced. I really love the fact that there’s always something unknown in science; it makes life a lot more interesting. Another thing I’ve learned is to always be analytical in terms of the information that is presented to us. We are taught to take everything as it is when we are young but there’s a huge shift of mentality when we start university. It’s a difficult change to make but it’s absolutely worth it. One final thing I’ve learned is that science is a struggle. Sometimes you just want to rip your hair out or destroy things but the sweet release and reward when you overcome that struggle is just so satisfying. When I first started my undergrad I never understood why people with graduate degrees were so proud of one figure they made in their paper, even if it took a year to make that figure. Now I understand that feeling of pride; there’s nothing else like it.

WEEK 11 LEARNING JOURNAL

1. Factual knowledge

Please describe, briefly, two new, distinct pieces of factual knowledge that you acquired or developed since the last learning journal

One piece of factual knowledge I have learned is that the long non-coding RNA called Xist inactivates the X chromosome from which it was transcribed and there are various factors like CTCF, Tsix, and Xite that regulate Xist. Another bit of factual knowledge I have acquired is that there are five potential models to explain how X chromosome inactivation begins: blocking factor, symmetry breaking, alternative states, transvection, and stochastic.

1. Conceptual knowledge

Since connections and models make for conceptual knowledge… please describe any connections (direct or indirect) that you can see between the two pieces of knowledge described in A.

CTCF, a binding factor which causes repression of Xist expression, is associated with the transvection model for X chromosome inactivation. The transvection model suggests that physical pairing interactions between homologous regions of X chromosomes allows signal exchange/communication between the two X chromosomes and eventually one X chromosome is shut down. CTCF is thought to aid in these pairing interactions. JPX RNA can target CTCF away from the Xist gene, allowing de-repression of Xist.

1. Metacognitive knowledge (no skills this time!)

If you are like most students in the class, you probably spent a significant amount of time reading, studying, and dissecting the article assigned for MT2.

1. Please describe, briefly, the strategy that you employed to complete the task.

I read the paper thoroughly once just to get a jist of the main points. Then I read the paper through a second time, carefully going through all the words or concepts that weren’t clear to me. I also wrote explanations in my own words for what each figure was showing and its importance.

2. Thinking about your experience with reading and dissecting this article, what was the hardest part?

I thought that generally the paper was really well laid out. I was very confused by some of the wording and I think that definitely could have been improved upon. I would’ve grasped this article much more quickly if the writing was better.

3. Thinking about your experience with reading and dissecting this article, what did you feel most comfortable with/confident about? Why do you think that is?

I was really comfortable and confident with interpreting the first few figures because the techniques used were familiar to me and they explained the reason behind their experiments. Even if they weren’t clear, the way they laid out their figures was very well-thought and I think it helped me grasp the important points of the paper really quickly. I definitely have to grapple with the logic behind why some experiments are done in other papers, but in this paper it wasn’t that big of an issue for me.

A.  Three things that stood out

Please describe, briefly, three things that you learned so far in BIOL463 and that really stood out to you (either because you enjoyed them, found them surprising, found them difficult – any reason).

            One thing that I learned recently is that non-coding RNAs such as AIR and Kc1qnot1 can prevent transcription of certain genes in cis. Air prevents the expression of paternal Slc22a3 while Kc1qnot1 prevents the expression of paternal Kcnq1. These are examples of genetic imprinting that can have some adverse effects in development. Another thing that I have learned is principle 6B: the three determinants of value are location, location, and location. It’s just so interesting to see through research that regulatory proteins such as Bicoid, Hunchback, Kruppel, and Giant are expressed at specfic timepoints in very specific locations; changing these locations or even preventing expression of these regulatory proteins can significantly divert development away from its normal path. In addition, I have also learned how important asymmetric distribution of maternal transcription factors/proteins is to the development of an embryo. If you don’t have asymmetric distribution of certain factors, there may not be any development to speak of. I thought that was really cool.

 B.  Identify types of knowledge

For each of your three “things”, please try to identify what type of knowledge it represents (Factual, Conceptual, Procedural/Skills, Metacognitive).

The non-coding RNAs AIR and Kcnq1ot1 preventing transcription is factual knowledge because there is research/evidence supporting this statement. Regulatory proteins such as Bicoid and Hunchback regulating development is also factual if you consider research that shows that these proteins are expressed in very specific locations within an embryo and knocking out these genes can alter development significantly. The asymmetric distribution of maternal factors being necessary for development is more conceptual because a lot of different examples can be encompassed by this statement. Since nothing specific is mentioned for this topic, it’s more of a concept than a fact.

 C.  What makes “things” stand out for you

For each of your three “things”, please indicate what made it stand out for you.

   All of the three topics mentioned here just makes me realize that development is so complex; so much has to go right for me to be able to be where I am right now. It makes my brain hurt just to try and think of all the mechanisms that must be involved. It would be interesting to see if someone could compile every single genetic mechanism that is necessary for one aspect of human development as we know it today. I would imagine this compilation would be larger than a collection of encyclopedias, maybe bigger than Wikipedia. What’s even more interesting is that there is more information coming in everyday and we might have to scrap some of our knowledge base because it’s just not accurate. This is why it stands out for me.

 D.  Evidence (of course, we are in a science course … we like evidence!)

Imagine that you need to test a group of students on one of your three “things”. Imagine that you need to determine, precisely, whether these students have acquired/developed the same knowledge that you have. How would you test them, and what would you consider as evidence that they have developed/acquired this knowledge?

1. Factual knowledge
2. Please describe, briefly, one new piece of factual knowledge that you acquired or developed so far in the BIOL463.

I have learned how maternal genes regulate gap genes, how gap genes regulate pair-rule genes, and how pair-rule genes regulate segment polarity genes. It was also very interesting to learn that gap genes can regulate other gap genes and pair-rule genes can regulate other pair-rule genes. It is amazing to see the intricate levels of regulation that goes into development. In particular, we learned that Bicoid and Giant interact with the eve2 enhancer and this interaction directs eve expression in stripe 2 of the Drosophila embryo.

2. Please describe how you know that you have acquired or developed this piece of factual knowledge, and provide some evidence for it.

Before the Feb 4th class started, Dr. Kalas drew a diagram of segment polarity regulation in Drosophila, which displayed everything I mentioned in the above question. In addition, we analyzed figures from the Arnosti et al. (1996) paper to draw conclusions about what the data represents. In this way, we were able to convert conceptual knowledge about gene regulation in Drosophila into factual knowledge (Bicoid and Giant regulate eve expression in stripe 2 of the Drosophila embryo.

1. Conceptual knowledge
2. Please describe, briefly, one new piece of conceptual knowledge that you acquired or developed so far in BIOL463.

I have learned that the collective techniques 3C, 4C, and 5C are great for determining which segments of a genome are closely interacting with each other. All three techniques use the same procedures initially but differ in the end; 3C requires qPCR, 4C requires inverse PCR, and 5C requires LMA.

2. Please describe how you know that you have acquired or developed this piece of conceptual knowledge, and provide some evidence for it.

During the techniques “speed-dating” session, I saw a presentation about the 3C, 4C, 5C techniques. This is still conceptual knowledge for me as I have never personally conducted these techniques nor can I verify whether these techniques are capable of providing of providing the results they are known for. Although many scientists have likely conducted and verified these techniques, I have yet to see the evidence; hence I consider it conceptual knowledge.

1. Skills
2. Please describe, briefly, one skill that you acquired or developed/are developing so far in BIOL463.

BIOL 463 is challenging me to develop my ability to critically analyze and question data that is put in front of me. This is a very valuable skill to have. I am excited to see how I can develop this skill further for the rest of this course.

2. Please describe how you know that you have acquired or developed this skill, and provide some evidence for it.

We are asked to analyze figures and draw conclusions rather than read explanations for what the figures indicate directly from the paper. We just did this with the Arnosti et al. (1996) paper where we analyzed the figures to determine which transcription factors regulate eve expression in stripe 2. If I was only asked to read the paper, I don’t think I would have gotten as much out of it. I think this is the best way to develop analytical skills in a research-based capacity and I look forward to doing more of this.

1. What is factual knowledge useful for?

Think about a piece of factual knowledge that you developed/acquired. Briefly describe what you think it is useful for.

                        From the Arnosti et al. paper, I have learned that Bicoid and Giant interacts with the eve2 enhancer and helps regulate eve expression in stripe 2 of the Drosophila embryo. This knowledge is useful for many reasons. It reiterates that Bicoid/Giant are important transcription factors for development. This information is also useful because it shows that gene regulation doesn’t occur with only one transcription factor or one level of regulation. Multiple modes of regulation (transcription factors) are required in specific combinations at specific locations within an embryo to direct the expression of a gene. Without this complexity, we wouldn’t exist. Finally, this knowledge is important because it can help elucidate other regulation mechanisms that dictate developmental patterns.

1. Factual knowledge
2. Please describe, briefly, one new piece of factual knowledge that you acquired or developed so far in the course.

Rspo2, a protein known to interact with Wnt to activate β-catenin, is required for cranial, facial, and left hind limb development in mice.

2. Please describe how you know that you have acquired or developed this piece of factual knowledge, and provide some evidence for it.

We were shown a figure from Yamada et al. (2009) paper which highlighted the type of information researchers can obtain from “removing something” experiments. The figure showed the differences in development between a mice strain which has WT Rspo2 and another strain with Rspo2 knocked-out. They determined that mice lacking Rspo2 had abnormal craniofacial development as well as poorly developed left hind limbs. The figure showed that Rspo2 is necessary for cranial, facial, and hind limb development in mice.

1. Conceptual knowledge
2. Please describe, briefly, one new piece of conceptual knowledge that you acquired or developed so far in the course.

I learned that there are four models to potentially explain how interactions between transcription factors and enhancers can mediate transcriptional silencing or activation. The four models are looping, tracking, linking, and facilitated tracking.

2. Please describe how you know that you have acquired or developed this piece of conceptual knowledge, and provide some evidence for it.

In class, we were talking about distinctions between enhancers, silencers, and boundary elements. When we came to the topic of enhancers, it became obvious that enhancers can significantly distant from the genes they regulate and there must be a mechanism to transmit information from enhancer interactions to regulatory regions of genes. These models were necessary to describe how this information is transmitted.

1. Skills
2. Please describe, briefly, one skill that you acquired or developed/are developing so far in the course.

I’m beginning to develop a more critical and analytical perspective in terms of what I’m reading. When we go over figures in class, I am starting to analyze figures as in-depth rather than accepting it as what it is. I’m learning to question why the authors chose to do a certain experiment and their logic behind their experimental design.

2. Please describe how you know that you have acquired or developed this skill, and provide some evidence for it.

Going over figures in class really helps me to develop a more analytical perspective on things. I have gone over many of the figures in class just like everyone has and sometimes it turns out that I understood some of the figure but maybe I missed on a minor point. Sometimes I may have even missed out on a critical point. Sometimes my fellow classmates will point out things that I didn’t see. I find this to be humbling but also really helpful because it makes me realize the level of attention and focus that is required in order to understand science papers properly. It’s also really good practice for whatever is coming next in my life.