Ways of Seeing: The Inner Life of the Cell

As part of my continuing series on how to visualise Biological concepts, allow me to delve for a bit into the inner life of the cell. Cells, small though they may be, are incredibly complicated things capable of performing a dizzying array of tasks to help keep itself, or the organism it is part of, alive. In order to take a closer look at how a cell normally functions, we’re going to have to start somewhere, and in this case, let’s start with the reception of a molecular signal by the cell.

When a molecular signal binds to a receptor on the outer surface of the cell membrane, the signal-ligand binding causes a conformational change in the shape of the receptor molecule, which causes the receptor molecule to trigger a cascade of biochemical reactions in the cytosol of the cell. Depending on the signalling mechanism, some signal molecules will induce the cell to begin the expression of a particular gene. When that happens, the transcription initiation complex will form around the promoter of the region and begin to transcribe a strand of pre-mRNA.

The pre-mRNA will then leave the nucleus via the nuclear pores to be spliced, capped and polyadenylated before being translated. Depending on the protein being synthesised, the mRNA strand is translated while freely suspended in the cytosol by the attachment of the small 40S subunit of the ribosome followed by the 60S ribosomal subunit to form the complete 80S ribosomal complex that translates the mRNA into a polypeptide sequence. In other cases, the same process occurs, albeit on the surface of the Rough Endoplasmic Reticulum (Rough ER), where the resultant polypeptide is synthesised directly into the lumen of the Rough ER in order for the protein product to be modified and packaged into vesicles for further repacking by the Golgi Apparatus. The vesicles leaving the Rough ER move to, and fuse with the cis face of the Golgi Apparatus, where the protein products are repacked and budded off as vesicles from the trans face of the Golgi Apparatus. The proteins in these secretory vesicles then go on to other compartments in the cell such as the cell membrane.

Well, that was a mouthful, wasn’t it? After having said all that, how much of the preceding 2 paragraphs were you able to internalise? My guess is probably very little, and I can understand why. Now let’s try something different. Take a look at the video below and tell me what you think:

The preceding video is the Siggraph Award winning animation titled The Inner Life of the Cell, created by a brilliant group called BioVisions over at Harvard University, and serves to highlight the usefulness of animations in illustrating biological concepts beyond what mere text can. By being able to ‘see’ the biological processes not just as a 2-dimensional drawing but as a dynamic series of processes occurring in a 3-dimensional space, the same principles introduced earlier in this post become easier to understand, and also go a long way toward aiding us in visualising the elegance of the cell’s inner workings.

The best part is, this isn’t the only such animated clip in the world. There lies out there in the internet, a massive treasure trove of biological animations just waiting to be watched and none of them will cost you a single cent. YouTube aside, both the McGraw Hill and W.H. Freeman websites are chock full of excellently made animations and interactive tutorials illustrating various biological concepts in a simple and accessible manner.

So there you have it; in the absence of simple ways for visualising biological concepts, animations aid in filling that gap by not only demonstrating how these reactions take place in a 3-dimensional space, but also by showing us how these individual reactions form part of a larger process aimed at effecting a specific cellular response. Do note, though, that the sites I’ve cited here are not the be all and end all of useful biological animations. If you know of any sites with particularly good content, please do share them with us in the comments section.

One last parting note: For those who are interested in seeing the full version of The Inner Life of the Cell with backing commentary, you can view that here:

This post will very definitely, almost certainly be made available on Student Oasis very soon

Ways of Seeing: Nervous Control

Nervous control is quite possibly the most nerve-racking (pardon the pun) topic in the entire ‘A’ Level Biology syllabus. Because the topic is so terribly abstract, many students often find grappling with the topic incredibly difficult and find recourse in memorising their lecture notes and textbooks wholesale (true story, I knew this guy who could recite Campbell from memory). As a result, the only thing students end up learning about nervous control is how to hate the topic with a vengeance, which makes further attempts at understanding it all the more frustrating and difficult. So what’s the secret to unlocking the mysteries of nervous control? Although different people rely on different methods to approach the topic, my method of choice is the age old practice of drawing diagrams.

Diagram drawing should not be new to most ‘A’ Level Biology students. It has been tested during the practical assessment component of the ‘O’ Level Biology course and is also an important skill for those who did the ‘O’ Level Geography course. The problem, however, is that most people do not realise that drawing diagrams is not just an examinable skill, it is also a powerful studying technique and an excellent way of visualising and revising concepts learned in class.

The key to drawing good diagrams is simplicity. You don’t have to be a master of the brush to draw good, effective diagrams that fully illustrate the concept in question. Take a neuron for example. Very simply, a neuron looks like this:

There is no need to add in any shading or colouring to add ‘depth’ or ‘character’ to your diagram, just use simple, clean lines to draw in the essential aspects of the concept in question.

Now that you’ve got a nice, simple diagram, the next step is to add some labels. While commonly overlooked, labelling your diagrams is pretty much the most important step in this whole process because it involves taking the facts that you have to internalise and matching them to the visual diagram that you’ve drawn. It is this process that helps you to remember the facts because of the visual context the diagram provides. In this way, not only do the facts become so much easier to visualise, they also become much more recallable, as compared to staring passively at someone else’s diagram in your textbook or lecture notes.

To be fair, however, not all the facts can be represented on the diagram without cluttering up your work beyond all visual recognition. As such, in order to provide a more complete picture, the last step is to annotate your diagram. Annotating your diagram is very much the same as taking notes, and involves writing down the remaining points significant to your diagram or a short paragraph explaining your diagram, usually in point form. When doing so, my advice is to keep your annotations simple and focused and avoid lifting points straight off your textbook or lecture notes. As far as possible, try to keep your annotations in your own words or your own voice so that it will be easier for you to personally understand.

With all that in the bag, what you will end up with is a clearer picture of how to understand the topic of neurons, as well as the added benefit of having made your own set of notes for revision. The topic of nervous control doesn’t just end there, of course, but with the techniques for drawing your own diagrams and making your own notes already at hand, you should have no difficulty using the skills discussed above to properly and visually represent the rest of the concepts in the theme of nervous control, and indeed for many other topics in Biology and other subjects.

For the benefit of those who still need more help, though, Let’s try to draw a diagram to explain the concept of ion exchange in maintaining the membrane potential across the axon membrane.

As can be seen from the diagram, there are embedded in the axon membrane transmembrane proteins that facilitate the transfer of Sodium (Na⁺) and Potassium (K⁺) ions across the membrane. One such protein is the sodium-potassium pump, that pumps Na⁺ ions out of the cell and K⁺ ions into the cell at a ratio of 3 Na⁺ ions going out for every 2 K⁺ ions coming in. As such, this establishes a negative charge on the inner surface of the cell membrane relative to the outer surface, which can be measured by a voltmeter across the membrane. This is called the membrane potential. In addition, there are 2 other proteins, the Voltage-gated Na⁺ channel and the Voltage-gated K⁺ channel. These proteins respond to changes in the membrane potential (the voltage) and will open and close to allow the respective ions through depending on the voltage across the axon membrane.

So as you can see, drawing clear, well labelled and well annotated diagrams can do plenty in helping you understand highly abstract topics. Not only does it help you visualise the concept, the act of drawing your own diagram versus looking at other people’s diagrams is similar to the effect of learning better by doing as opposed to just reading about it – the experience of drawing helps to make remembering easier.

Do bear in mind, though, that this is not the only method that can be applied in understanding nervous control or any other topic in the Biology syllabus for that matter, and the only reason why I’ve used this method here is because it happens to work particularly well for me and perhaps it might for you too.

On a separate note, the diagrams shown here were all taken from a set of notes that I’ve written myself during my JC days, and you can view the full thing by clicking on the thumbnail below.

This post will be up on Student Oasis soon…

Ways of Seeing: Phosphorylation

As mentioned in my earlier post, one of the most powerful ways of understanding Biology is to be able to visualise concepts. In this post, I will be demonstrating a powerful way of looking at, and understanding what is arguably one of the most important biochemical reactions in all living organisms: Phosphorylation.

We’ve all heard of phosphorylation from Biology lectures. The process of attaching a molecule of inorganic phosphate (PO₄^3-) to another molecule, whether it is glucose or an enzyme such as p53, is a hugely important process that has massive implications for how the cell operates, and consequently how the entire organism functions. For enzymes, in particular, phosphorylation serves as a form of biochemical ‘on/off’ switch, with the ability to ‘activate’ or ‘deactivate’ an enzyme’s function and trigger a biochemical chain reaction resulting in one or many outcomes ranging from elevated expression of a particular gene to apoptosis (cellular suicide). Most of us students know what phosphorylation can do, but do we know why or how?

In order to properly understand phosphorylation, we must first look at the molecule behind it all: the PO₄^3- ion.

The PO₄^3- ion is an incredibly highly charged molecule, with a single atom of Phosphorous surrounded by 4 atoms of one of the most electronegative elements in the periodic table – Oxygen. Although the 3- charge held by PO₄^3- might not sound like much, chemically speaking, a charge with a magnitude of 3 is an immensely powerful one. The Al3+ ion, for instance, is so highly charged that it immediately polarises surrounding water molecules to form the [Al(H2O)6]3+ complex instead of remaining on its own. As such, PO₄^3- is in essence a highly electronegative and negatively charged ion, a ball of negativity, if you will.

Now that we know what PO₄^3- is like, let’s turn to the enzyme molecules that PO₄^3- often finds itself attached to. For the purposes of this illustration, I’ll be using p53, the tumour suppressor protein, as an example. All enzymes, as we know, are proteins, and all proteins are essentially folded chains of amino acids. There are 20 naturally occurring amino acids and each of them has the basic structure of where R is a side chain that can range from a simple Hydrogen atom (in Glycine) to a benzene ring (in Phenylalanine). These side chains are what differentiates one amino acid from another and as a consequence, each amino acid displays a different electron distribution and density.

Now how does this electron distribution affect p53? For this, we’ll need the help of a special software called PyMOL, which can be downloaded for free here. PyMOL is a software that allows us to view macromolecules such as proteins and DNA and is often used by scientists for demonstrative or analytical purposes. In addition to PyMOL, we’ll also have to download the file for p53 from the Protein Data Bank (PDB), which is an online archive of proteins, DNA and other complex structures.

Once you’ve installed PyMOL, open the p53 file using PyMOL and you will be treated to the sight of a p53 molecule bound to a short strand of DNA:Using your mouse, you can click and drag to move the protein molecule around. In addition, you can also play around with the settings to view the molecule in a variety of ways such as a ‘ball-and-stick’ model or in cartoon form. For the purposes of this demonstration, however, I will only be using the ‘generate vacuum electrostatics’ function, which is shown in the picture belowDo be patient while the software computes and generates out the vacuum electrostatics view of the protein molecule. When the process is done, this is what you should see (do note that the DNA strand is not included in the electrostatic model):

What this view shows us is the charge distribution across the entire p53 molecule in a vacuum. The red regions represent areas of negative polarity while the blue regions represent areas of positive polarity and the white regions are neutral – neither positive nor negatively charged.

So what happens when a PO₄^3- ion is attached to one of the blue or red regions when p53 is in its inactive state? Because PO₄^3- is such a negatively charged molecule, the attachment of a PO₄^3- molecule to either the blue or red regions on the p53 molecule will result in either repulsion or attraction. This repulsive or attractive force, in return, will alter the shape of the p53 molecule. This conformational change in the enzyme’s shape causes the shape of the active site, the catalytic region of the enzyme, to change its shape to be able to accommodate the shape of p53′s target substrate. When p53 is able to bind to its target substrate (i.e. DNA), it can thus perform its function as an anti-cancer, tumour suppressing enzyme.

As you can see, with the aid of a few diagrams and visualisation techniques, we are able to gain a better and clearer picture of how phosphorylation works and why it is so important. Of course, protein activation is not the only effect of phosphorylation (the phosphorylation of glucose in glycolysis serves a completely different purpose), but once you are aware of the importance of the charged nature of PO₄^3-, I’m sure you’ll be able to deduce for yourself the significance of phosphorylation as a process in general.

This post will soon be posted on Student Oasis