Wednesday, 6 March 2013

A Dynamic System of Accetylating and Deaccetylating Factors Has Effects on Transcription


Specific sequences in DNA recruit transcription factors, called activators and repessors, coactivators and corepressors. In order for DNA to be transcribed and expressed, the chromatin needs to be decondensed (accetylated) to allow for there to be enough space for these transcription factors to bind. For a transcription factor to bind, it binds to a histone acetyl-transferase, which unfolds the chromatin.

However, either side of the recruitment position has deacetylating enzymes. This creates a battle of kinetics and equilibrium shifts, where the two forces of accetylation and deacetylation are competing to determine the outcome of whether or not the transcription factor can bind to the region. Also, the success of transcription depends on how long the transcription factor can bind. If the factor is easily displaced, transcription cannot occur.

It is possible for heterochromatin to have an activator bind to a promoter, but it is less probable because of reaction kinetics. In the lab, if decondensation is required for a highly deaccetylated region, viral components are used to induce this process.

There are other chromatin modifications, which contribute to a histone code. The histones are modified in different ways to alter the charge and the overall surface of the protein, which effects the binding properties. Common alterations include phosphorylation, mono-ubiquitination, and methylation.

Phosphorylation, mono-ubiquitination, and methylation lead to either activation or repression of the gene depending on location of the modification. If we examine more closely the effects of methylation in particular, the properties of the three methyl groups bound to the histone cause the amine function to be blocked, and the positive charge to be maintained. This, in turn, blocks acetylation, which means the chromatin in that region will be condensed, and it is unlikely transcription will occurs.

Each of the histone modification reactions is reversible and carried out by enzymes.

In addition to the above methods to modify chromatin structure, chromatin remodeling mediated by chromatin remodeling complexes also is possible. The complexes detach the strong interactions of the histones with the DNA, in a way that does not completely remove them, but makes the DNA more accessible.

The process of initiating transcription is dynamically controlled by access to the DNA regions and how tightly the chromatin is bound.

Note:
Recall that acetylation is when the lysine residues in histones are bound to an acetyl group, making the positive amino acid neutral. This prevents the interaction of the histones with the negative phosphate backbone of the DNA, and the chromatin is decondensed, allowing easier access for transcription factors to bind, and gene expression to take place. On the other hand, deaccetylated histones do not have the acetyl group bound, and the lysine residues maintain their positive charge and are attracted to the phosphate backbone of the DNA, causing the chromatin to be condensed, and reducing expression.

Tuesday, 12 February 2013

Gastrointestinal Tract Poetry

One of the most charming professors at McGill University is Dr. Ann Wechsler, with her pleasant manner, and lectures full of not only facts, but also encouragement. Last semester, she coordinated the first introductory physiology class, and wrote many poems that eloquently and concisely summarized concepts. Truly, she is a gem of an instructor, and I have heard nothing but compliments from other students describing her teaching.

So, naturally, when she returned to the second semester of introductory physiology, I asked her if there would be any poems that day. She informed me that I could write a poem for the Wednesday lecture summarizing the Monday lecture content. And so, honoured, I did.

If you look into the deep past of this blog, you will find some ancient poetry written recreationally for high school and some university classes, mainly to amuse my peers. Lately, I haven't been writing much academic poetry, as the content is more technical, so double entendres become more difficult to incorporate. However, I did my best, and I hope you will enjoy reading this poem as much as I enjoyed writing it!


To absorb information of the Gastrointestinal Tract
We must digest thoroughly for maximum impact!
It developed from a tube passing straight through
To a larger structure with differentiated tissue.
At four point five meters it certainly isn’t short,
With surface area extending an entire tennis court.
The serosa is a layer tough, but thin in style,
Where as the muscularis externa is versatile,
With fibers either parallel or angled to the right,
And skeletal and smooth; then the submucosa site,
Which covered in loose connective tissue and nerves,
Underneath the mucosae with three layers deserves
To be mentioned, with muscularis mucosae smoothly designed
And lamina propria with loose connective tissue defined.
And lastly the business end, the single epithelial layer
With its endocrine and exocrine functions is a key player.
But what about the major functions of the GIT?
We have secretion, absorption, and motility!
The saying to think with your stomach is correct,
As the enteric enervation certainly does connect
An assemble of elements for a complete reflex arc:
Many action potentials together with algebraic spark.
Both autonomic systems together regulate
The enteric nerves and their cumulative fate,
As ACh excites a neuron’s respective role
Be it to activate or inhibit the signal as a whole;
Where as NA does the opposite, the role it prohibits
And excites enteric neuron which ACh inhibits.
The enteric neurons that inhibit release NANC,
And those that release ACh are excitatory.
This signals either a secretory or smooth muscle cell
And if this seems rather complicated – well,
I admit this poem summarizes quite a lot,
Because after all, it serves as food for thought! 

Friday, 25 January 2013

It's All Greek to Me

When I spoke to an advisor about my schedule for the new semester, she looked over my selected courses, and verified that yes, indeed they were required for my 2nd year of my physiology program, and they would stand me in good stead for completing my degree. However, when the advisor came to the mysterious course code of CLAS220-D2-001, there was an audible sigh from her side of the desk. I braced myself, as I knew the inevitable was coming.

"Why Ancient Greek?" she asked. 

This question has been posed from my colleagues in my physiology lecture, my mystified parents, and any advisor I set sights on the McGill campus. Clearly, Ancient Greek is not a prerequisite for any upper level physiology course, and the vocabulary I learn from hoplites to the marvellous verb "to be a choral dancer," does not always directly relate to origins of scientific nomenclature. But, over this past year I have heard many different stories from students in my classes, about their electives. And maybe the question should be changed to: 

"Why East Asian Cultural Studies?"
"Why French?"
"Why Art of Listening?"
"Why Greek Mythology?" 
"Why Gifted Students?" 
"Why Linguistics?" 

And then, to form a general over-arching question of the above: 

"Why take an elective that does not directly relate to the course requirements to your degree? Especially an Arts Elective?"

In response:
Why bother to attend a university if you are not inquisitive and love to learn? Why should your interests be limited to your degree? Are you not a human being and above all a human being before you are a developing scientist? Do not the different disciplines work together to create a cohesive education that enhances the human experience? 

To further answer the question, "Why Ancient Greek?" and to encourage other science undergraduates to explore a minor that will be enjoyable and complement their core courses, I have included several reasons below from my classes this year in Introductory Ancient Greek as well as last year's elective Introductory Latin. 

1) Smaller Class Sizes 

The undergraduate science large class sizes of first and second year with 600 people are intimidating. Even if you sit with the same people everyday, it is difficult to hold conversations, let alone approach the professor. If you participate in lecture, it is not practical for everyone be active every class, otherwise the hour long lecture would be a continuous stream of questions punctuated by a 5 minute theory section by the professor. The feeling of anonymity is high. 

In both of my Ancient Greek and Latin classes, the professor knew my name by the end of the first lecture, and I met at least three people around me. Immediately, the feeling in the class is more intimate. From each of the quizzes, the professor is well-aware of the common mistakes of each of the 20 students, and can direct the lecture to address your needs. Also, many times the professor notices your mood each class. He/she may comment that a particular student looks particularly tired that day, or if a student does usually poorly on a quiz, may ask after the student's health and schedule from that week. This type of concern has not happened only to me, but to many of my other classmates. The relationship between the classics professor and student on a class by class basis is more nurturing than even with the best professor in an introductory course in the sciences. 

2) Communicative Skills and Group Work

Arguably, in science courses, we obtain practice communicating with different lab partners for each experiment of the semester. However, this type of job is more qualitative as it primarily involves measurements, task distribution, and results interpretation. In a classical language class, much time is spent in groups translating texts. Not only do you gain an appreciation for the differences between english and ancient greek/latin, and how to express oneself more concisely, but also the dialogue involves collaboration between parties about how best to translate the passage. The flavouring and nuances of the translation leads to better knowledge of how to communicate using one's primary language, as well as the second language of study. As a group you become aware of your strengths in both languages as well as your weakness, and you are able to consult the group "expert on clauses" or the group "expert on verb forms" as each part of the sentence occurs. (Note that neither latin or ancient greek requires the student to be able to speak the language, merely read and write it, as the courses are translation driven.) 

3) Appreciation of the Evolution of Language and the Human Mind

The comparison between latin/ancient greek and english reveals the difference between their respective syntax and vocabulary. Since nouns decline in both greek and latin (the noun changes form based on its grammatical role, such as subject or direct object, in a sentence), this shows a greater precision than english. The literary devices that can be used from different grammatical forms, suggests variation in how human beings were thinking during that point in history from today's world. Also, the composition of language reflects the wonder of the human brain, and how it can innately create such culturally varied methods of communication. 

4) Occasional References to Science Courses

Yes, as my science friends like to joke, at least I can recognize every greek letter that appears in our formulae! But beyond this, it can be a memorization tool when the odd vocabulary word overlaps from a classical language class to a science course. The word that comes most readily to mind was introduced in physical chemistry, endergonic and exergonic, where ergos in Ancient Greek means work. More obviously, perhaps, is perimeter, with the prefix peri meaning through. To be a little more complex we have the word paragraph, with para as the Ancient Greek prefix for beside, and graph from the verb grapho, to write. And of course, to be obscure, the ambulocetus, from the latin verb ambulo , to walk. 

the ambulocetus, in case you were curious

5) It Makes a Great Conversation Starter

To my nonscientific family and friends, if I tell them my courses from last semester, they fondly tell me they sound all the same. "Organic chemistry, physical chemistry, molecular biology, physiology" and  they do have a poetic ring together in a list. But Ancient Greek or Latin? Everyone remembers it and wants to talk to you about it. I'm not sure entirely why this is, but the nonscientific crowd tells me that it is cool. I think the science courses make you cooler, but whatever, somehow the general public seems to relate to dead languages more than DNA. Go figure. 

6) The Professor Will Never Ask "Why Ancient Greek?" 

Out of all of the people who deal with you about taking a classical language, the one person who will not question your motives and you is your biggest supporter (from my experience) is actually your professor. When I was having a hard time with organic chemistry last semester, I ranted to my Ancient Greek Professor about my frustration, and she told me, "When I took organic chemistry, it was my least favourite course. But suddenly it all started to make sense, and it became my favourite." 

Now, I was flabbergasted. If there was anyone anti-organic chem, I expected them to be my Ancient Greek Professor, but that someone who was not using the course could still remember it to be worthwhile and to have provided a reward of joy out of the initial struggle - well! These words inspired me more than my organic chemistry professor ever could have! (Although my organic chemistry professor from last term is my role model and when I grow up I would like to be just like her, minus studying chemistry!) And, I am happy to say that my Greek Professor was right in her prediction, and by the end, organic chemistry and I did manage to get along quite nicely too. 


Now, after a long-winded justification, I hope that I have provided an explanation for those who question why science undergraduates take arts courses, and why electives are an integral part of a good university education. 

If you are wondering whether one of these courses is right for you, feel free to contact me. I do however, recommend taking Latin first as it doesn't have a different alphabet and accents to grapple with, and so it allows you to get a better idea of the grammar and syntax.