S377: The exam

The exam - and one I have not been looking forward to.
There are just so many things that they can test you on here, it seems impossible to revise everything. Some things seems to come up regularly. Cancer, and cell structural proteins - but they are both quite big subjects.
Others seem to come up at random.

The format is to do eight questions out of 12 in the first part - all of these worth 10 points. Then answer questions on a research paper that you have been given beforehand for the remaining 20 points.

Q1 is about the microfilament network. I'm better on the microtubule network, but I gave this a go.

Q2 looked horrendous, asking you to draw a sketch graph of the activation energy of an enzyme catalysed reaction. After reflecting on it for a bit though - I decided this was really just the same as a normal chemical reaction graph that I'd done in S205. I'm hoping so anyway - so tried that too. Also covered SDM and catalytic sites.

Q3 was about membrane proteins and included secondary and tertiary structure questions. I tried this one too.

Q4 was about eukaryotic nucleosomes and apoptosis. I tried this, but really couldn't remember half the proteins involved (well half is probably an overstatement - I don't think I got any of them - until I was walking down the street after the exam!).

Q5 was about mRNA splicing and the removal of introns. It also covered RNAi methods - I tried this, but again couldn't remember the relevant proteins.

Q6 was about ribosomes, and I tried this working from first principles. I knew how they worked, but hadn't revised any of the details, so I sort of shot in the dark for the explanations they required.

Q7 was about RTK signalling receptors. I had revised this - but not quite in the form the question was asking. I scratched around - trawled my memory, and guessed at some of it.

Q8 was about apoptosis and necrosis, and a bit about tumour development. I tried this too.

Q9 was about tumour development - but I couldn't remember the techniques they asked about. I think I skipped this one

Q10 was about small G proteins, RAS and VEGF. I tried this one too.

Q11 was about ageing and mitochondria. I might have attempted this - I can't remember. I wouldn't have got far if so.

Q12 was about stem cells, intestinal cells and the WNT pathway. I couldn't remember enough detail to attempt this one.

The paper is a bit of a shock to most of us. Not so many of the common topics seem to come up, and quite a few oddities come out of the woodwork in the first part. Stuff that hasn't been on previous years papers and I think many of us were scratching around for things we could answer. In the end I did manage to find 8 questions to answer, but some of them rather badly. It was good in that the first question I could answer, but then as I scanned down the paper, circling those I might try, I'd got to the last question and only ringed about 3, and some of those rather hesitantly. At the end I attempted a couple more questions as I had lots of time spare, to see if I fared any better.

In contrast the research paper seemed a lot nicer - there were a couple of questions that had to be answered with knowledge from the course, rather than digging out figures and things.

So all in all - a bit of a shock and although it was never going to be an easy paper - it was harder than most of us were expecting I think.

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S377: TMA-4

TMA-4  - the last one.

Question 1 - and we're back to ICAMs. This time interaction with other molecules and cells such as T-lymphocytes. It also goes into signalling with chemokines and things like that.

Question 2 - we;re into differentiation starting with embryos. This includes going through the different mechanisms and drawing a picture for asymmetric division. Then some discussion of how possible antibodies could distort the division and what its effect might be.

Question 3  looks at the enzyme G3PDH, two versions of it. One human the other lobster. First it has to be displayed with its active site visible and showing the interactions.

Then there is a list of comparisons to be done, to compare the amino acids between the two different forms, and show how much conservation there is in the structure. You also have to predict what effect changing some of the AA might do to the activity of the protein.

Question 4 and you have to write a report based on some virtual experiments. Its not quite the normal scientific paper I've come to know that they are asking for, but something similar. There are quite tight constraints on it though. Only 4 pages, a max of 800 word, max 1 table and 1-2 figures. So emphasis on conciseness.

Slightly better marks for this one - but overall lower than I'd hoped across the whole course.

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S377: TMA-3

It's time for TMA-3.

So 5 questions to be answered.

Question one is about endocytosis. It gives you 5 different things that are endocytosed, and asks you for the different mechanisms they use. These are IgA, transferrin, influenza virus, apoptotic cell debris and cholera toxin - so there.

Question 2 looks at the cell surface ICAM-1 in rather more detail than I ever want to again. How it is glycosylated and how it is transported about the cell, and all the key proteins it comes into contact with.

Question 3 - more on ICAM this time on its signalling system. What class of receptor it is, how it might function and its processes within the system.

Question 4 is about caspases and death domains, apoptosis and the like. I can't help thinking of death eaters from harry potter for some reason all the way through this.

Question 5 we have another paper to study, about altzeimers and untranslated regions of the mRNA. It looks in detail about mRNA regulation, and that there are mechanisms to stop the translation of mRNA into protein that can react quickly to needs. Anyway, there is a huge number of questions on this - a) to m), and several of these having i) ii) iii) subparts. There are a lot of marks on offer for this (50%). I manage to lose quite a few here though, and nto through not understanding, just being slightly out of kilter with exactly what the question is asking for. I think several of my answers are sort of right, but not what is expected. Grrr. My worst score so far.

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S377: Book 4 (The Interactive Cell)

Book 4 - the final book in the course.

It starts with a short chapter (15) on cellular interaction. Just a few pages long and a sort of introduction.

Then onto chapter 16 about Cell Migration and Adhesion. Looks at the various cell adhesion molecules, cell movement, chemotaxis and control. Also disintegrins and a few other bits and pieces.

Chapter 17 is about differentiation, how a single cell can grow into a multicellular organism. What different ways growth and differentiation is controlled, and how nerve systems and other organs develop.

Chapter 18 is the other end of the cycle so to speak. It looks at cell death, ageing and damage. It looks at a number of ways ageing may occur, and concludes it is probably multi-faceted.

Chapter 19 is the last part, and looks at tumorigenesis. This sort of brings lots of things together, becase for tumours to come about a number of the pathways and mechanisms have to fail. So some of the pathways get stuck in the on position. Some of the checks get switched off. Cells migrate away from their location spreading the tumour. They have to avoid the apoptotic signals that would otherwise kill them, become immortal and grow without limit whiles maintaining blood supply. So a lot of things have to happen to get to the final part.

So - I suppose its a good round up, but not always the sort of thing you want to read about.

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S377: TMA-2

So TMA-2 of the course. Five questions.

The first one is about mitosis, and the anaphase part. You have to draw a diagram of a cell on the verge of splitting its chromosomes. Then talk about the proteins involved in the separation and the conditions required to bring about the separatation. Then a bit to answer on what happens if any of the mechanisms fail.

The next question is about DNA replication and how it happens, what speed it goes at and how it differs between eukaryotes and prokaryotes. Also a classic experiment on the process is investigated to explain how it works.

Question 3 is about transcription. It considers the TATA box, and how transcription factors are involved. Then the epigenetic DNA modifications and how they are preserved.

Question 4 you have to investigate a zinc finger transcription factor and look into the structure of it. How the metal ions are held, and how it interacts with the DNA molecule. Finally you have to show part of the model with some parts highlighted in colour and labelled.

Question 5 you have a paper about a membrane bound protein, and there are a whole load of questions on it. Some is stuff from the course, other is data from the paper. There are a lot of questions, and I found it easy to get out of step answering a little too much in a) and then not including some of the data in b) so losing marks.

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S377: Book 3 - The Dynamic Cell (Vol 2)

Book 3 which is confusingly entitled The Dynamic Cell - Volume 2 carries on from the previous book.
There are just three chapters in this, although some of them are pretty big.

Cpater 12 Transport and Compartmentalization: It starts with a chapter on transport and compartmentalisation. This covers how the cell moves stuff around, how signal in the code are recognised as labels to send the packages to the correct destination. It also looks at hte transport network, which moves these vesicles around. It covers endocytosis (bringing stuff into the cell) and exocytosis - the opposite. 64 pages in this chapter!

Chapter 13 Signal Transduction: The next chapter is about signal transduction. How signal are recognised on the cell surface and how they trigger cascades. Also some words on the different receptors and ligands that are in common usage.

Chapter 14 Cell Death: The final chapter is on the subject of cell death. All cells have the ability to commit suicide, either on command or if they detect things are going wrong. So this chapter covers some of the mechanisms that trigger these events.

So 180 pages or so in this book.  Some of it is pretty heavy going, but interesting.

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S377: Book 2 - The Dynamic Cell (Vol 1)

This is the 2nd book of the S377 course.

We start to get into a lot of the cellular stuff here. The chapter numbers follow on from the first book - so it starts with Chapter 7.

Chapter 7 - Introducing the Dynamic Cell is quite brief, and is an introduction to the cell and its contents. Nothing particularly new here, but it sets the scene.

Chapter 8 - The Cell Cycle is much more in depth. We cover the mechanisms of mitosis, the cell cycle meiosis and cell division. However this is in quite gory detail. I'm sure many people have seen videos of chromosomes lining up and then separating to opposite ends of the cell. All very nice, I've even seen it under the microscope, although of cells caught in the act rather than dynamic. However you have to ask here, how do the chromosomes move around, how do they pair up, how do they line up? What causes them to separate and how does the cell arrange for it to happen without error.

Chapter 9 - DNA Replication and Repair - again something I've covered many times before. However not in this detail. The typical animated image shows DNA unzipping and getting copied just like that. However its a lot more complicated than that. For instance as the strands separate under the influence of a enzyme, the twisted nature of DNA means that further up the molecule it starts to get all twisted and under tension . Its like unwinding the strands of string, as you pull them apart if starts to ravel up further down. DNA is also often packed up into compact structures, which have to be unpacked before you can even start the replication. Then there is the problem of replicating the lagging strand, the fact that to replicate something like human DNA in any reasonable time you have to have lots of replication at the same time doing different bits, that then all have to get joined together. Yes - its complicated. Then there is repair...

Chapter 10 - Gene Expression - this chapter is all about how genes are switched on and off. Lots of stuff on operon, enhancers, silencers and so on. The infamous Trp operon is considered.

Chapter 11 - Translation and Protein Turnover - the last chapter of this book. Considers how the ribosomes work, how they match the tRNA to the mRNA, and how the tRNA gets the right amino acid attached to itself - again something normally skated over. There is also alternate splicing, mRNA regulation, post transcription modification, nuclear export - lots of details here.

Some fascinating stuff here - and some stuff that is not too well understood.

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S377: TMA-1

The first TMA of the course - and its a long time until the submission date. Given I started the reading before Christmas, the April submission date is a long way in, and I've read past most of the relevant material, so some rereading is required.

So there are 5 questions to answer.

Question 1 is about enzyme structure. It looks at a kinase and you have to make some general comments on structure, domains and function.

In Question 2 we have to look at a 3-d molecular model and identify and measure parts of it. There are also tasks to perform. Also required is to include an image of the enzyme active site.

Question 3 simply gives you some concentration data and asks you to work out the equilibrium dissociation coefficient of a ligand and its receptor. The question is a little sparse as it doesn't really give much guidance on what is wanted in the answer except the value.

Question 4 is about SDS-PAGE and requires you to run gels on the computer simulation with a number of kinases and antibodies to work out what the results tell you.

Question 5 is all about reading scientific literature. You are given a piece of writing and then have to make sense of it and answer a number of questions about what its conclusions are.

Not a bad TMA in some ways - but a little disappointed with the mark I get.

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S377: Book 1 - From Molecules to Cells

Book 1, being the first book therein, is, as indeed is conventional, is the first book in the course. So its where you start into this course. At just over 300 pages its a reasonably large book - but one of four that make up this course. So - plunging in what do we find inside.

Chapter 1, Evolution of the cell, is really a sort of introduction, but describes the probable evolution of the biological cell. It's a nice short chapter with plenty of familiar terminology and concepts - so is a reasonable introduction into things.

Chapter 2, The foundations of life, is a tad more involved. It considers a lot of chemistry that makes up the cell, including the chemistry of water, biological carbon compounds and ions. There is a fair bit on different types of bonding, chemical equilibria, stereochemistry, pH and pK factors, and the interaction between molecules. There is also a section on molecular modelling and getting you to use the 3-d programs that display molecules to become familiar with it and its abilities. So quite a lot of chemistry in this chapter, which would be a lot of new things to contend with if I hadn't done the S205 course.

Chapter 3, Proteins, goes into a lot of detail about proteins. It looks at electrical interactions of the side chains of amino acids, protein domains and families. There is more on molecular modelling 3-d program too and its ability to show the tertiary and quaternary structures of proteins - as well as the atoms.

Chapter 4, Thermodynamics and Bioenergetics, looks in detail at some of the thermodynamic principles as to whether reactions will proceed or not. This culminates in discussions of Gibbs free energy and entropy/enthalpy, which is second nature after S205 - although the application to biological molecules is a little more complex.

Chapter 5, Nucleic acids and chromatin, considers the key genetic molecules and spends some time looking at their structures. DNA can be found in its traditional double helix, but also in two other forms. It also looks at other forms of the nucleic acids and how their packaging in increasingly complex structures which reduce potential damage. Again some chemistry comes into this as it looks at energetically favourable states.

Chapter 6, Membranes, looks at the structure of membranes and the various components they can be made of. It considers the different types of fatty acids and what they bring to membrane structure. It also looks at the proteins that attach to membranes in their various forms.

Also at points in this book you are directed to read some scientific papers, including the original Watson and Crick DNA paper, and their follow up which gives detail of the proposed structure.

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S377: Molecular and Cell Biology - Arrival

The next course arrives - it doesn't start until February, but I'm doing two courses together, so I'm glad of the head start. This is only the first of two mailings, but has some good stuff in it.

What you get is:

• Book 1 - From molecule to cell
• Book 2 - The Dynamic Cell (Vol 1)
• A Bookmark with some useful data about amino acids on
• A ring binder
• A ring binder insert with pretty picture and title
• A set of folder dividers
• A glossary
• An introduction and guide
• A study skills pack for books 1 and 2
• A DVD containing molecular modelling programs, movies and other bits

Notable by their absence is a calendar, TMAs and the normal OU computer disk.

All looks nice and shiny, and I'm ready to go having not had any assignments to do for the last month or so. However as the course site doesn't open for a while yet, there are no assignments to contemplate, just books to read and exercises to do.

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