How to become a scientist

This post was first published in Jump! an online magazine for pre-teen girls.

Science is fun

What scientists do on holiday

To become a scientist you must first, take an enquiring mind, blend it with some passion, sprinkle on some creativity. Mix it up a bit, and squirt it out in big, loud dollops for everyone to see.

Science is not just for geeks and nerds. It’s not only for boys, or girls, who wear glasses. It’s for those of us with freckles and dimples and turned-up noses. Science is for animal lovers, tongue-rollers, bird-watchers, and teddy bear vets everywhere.

You see science is the world. And we are the world. So science is us, humans.

I love all science, but I especially love human science. The kind of science that looks under your skin, inside your cells, and zooms in, right down to your genes. This is what makes us human, and each one of us is unique and exciting.

I became a scientist because I was inspired to by a biology teacher at school. She asked me to help her clear out the cupboard in the lab. What we didn’t find in there. And lurking at the back, in a dark jar, was the most gorgeous pig foetus. We changed the preserving fluid, to reveal the tiny, perfect animal; when was he put in there, kept for me to find? I was hooked.

At university I studied human anatomy. I was able to study bodies donated to medical research, to look inside each and every part of the body, to learn where everything goes and how everything fits perfectly together. We prepared glass slides of the microanatomy too. We studied how the cells in the body connect to each other and to the rest of the body. It was fascinating study.

In my work since, I have used this knowledge of the human body every day. Every single experiment we carry out, is done in the knowledge that someday, somewhere, someone will one day benefit from the work we are doing to find out more about the genes which control all aspects of human life and variety.

Interested?

If you want to read a bit more, the next two sections are more advanced, but I’m sure you’ll be able to follow.

DNA unwound

DNA is fascinating. I have spent nearly twenty years getting inside this dynamic molecule, the basic component of human life, that controls hair colour and how long you will live and everything in between.

Laboratory analysis of DNA

Every cell in the human body contains this miracle molecule. It's wound up inside the nucleus and can respond to our changing environment. For example, in work I have recently completed, I have been able to measure the rate of response of DNA to conditions mimicking inflammation in the wall of the peripheral blood vessels. Put simply, I created a laboratory model of atherosclerosis, which as you know is a thickening of the arteries, leading to heart attack and stroke. These experiments were important to do because they showed us how the DNA functions in cells from individual people with different DNA variations.

DNA is divided into functional regions, which we call genes. These genes contain naturally occurring variations, which makes us different from one another. Many of these variants are completely compatible with normal life; that is, the cell will grow and divide in the normal way. This is different from mutations such as those in cancerous cells, which cause aberrant cell proliferation and division.

In order for a region of DNA to respond to a signal from outside the cell, it must be in a relaxed or open state. A number of carrier or transport molecules including cytokines are responsible for presenting the stimulus to the open DNA molecule, in the correct functional position or gene. Once this has happened, the region of DNA closes, a bit like pushing a spring between your hands. In this closed the position, the function of the gene is turned off and no other molecules can interact with the DNA. Imagine a very fine orchestra with a very busy conductor making sure that nothing goes out of tune. All these processes happen without our conscious intervention, and that is what makes DNA fascinating.

Human macrophages, from white blood cells

Techniques developed in the laboratory by some very clever scientists have allowed us to visualise these processes. We can measure them and discern differences in them between different people, who have different gene variants. Thus, we can say that genetics can determine an individual's response to inflammation. But what do we do with this information. Well, in the not too distant future scientists would like to translate this research into the clinical setting so that family and hospital doctors may be able to look at our genetics when deciding on treatment.

Cellular communication

No, nothing to do with a cell phone, because before mobiles or cell phones there was a time when this only meant cell to cell interaction within an organ or tissue. This important cellular behaviour drives diverse functions from contracting myocytes in heart muscle to effecting action potentials in nerves.

We can visualise these fascinating events in the laboratory ex vivo (in cells outside of a living body). For example, immortalised cardiac myocytes (heart muscle cells kept alive) can be cultured in a monolayer in a petri dish. A stimulant introduced into a single cell causes that cell to contract. This stimulates the adjacent cell to contract, and so on, mimicking the heartbeat. This can be seen microscopically and contributes to our better understanding of the function of this important tissue.

Cross section through mitochondrion,
a part of the cell which makes energy

Similarly, action potentials in nervous tissue can be measured and studied by subjecting ultra-thin sections of tissue to chemical modulators in solution. Sensitive electrophysiology equipment detects the release of neurotransmitters from neurons in the tissue slice and complex algorithms translate this effect into an audible thump. It's really amazing to hear this happening in the lab, these are very elegant experiments indeed.

A different kind of communication is seen in the immune system, where antigen-presenting cells identify foreign bodies, such as bacteria, and 'show' them to the T lymphocyte cells which effect an immune response. Where this system is compromised or overwhelmed, an infection can set in, for example pneumonia, which requires a trip to the doctor for antibiotics.

And who said biology was just a pretty face?

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I met a man who asked me about quantum mechanics of DNA...

Not your standard black tie dinner party conversation, Jonathan, but I can talk about anything. Of course DNA structure and function are governed by the laws of physics, bonds must be obeyed, physical restraints respected, spatial integrity maintained. That's at the very heart of chromatin remodelling. Now, I had planned to write next about RNA, but this conversation reminded me that most amateur molecular biologists imagine that DNA is a linear molecule and everything happens along a long, flat line. That's not true. Firstly, you should all know that DNA is in fact double-stranded. Secondly, the bonds between the bases cause a torsion or twist, known as the helix. The entire double-stranded DNA helix is further wound around histones (ordered clumps of proteins), which adds another layer of constraint. And all of this is packed into the nucleus of the cell. Brilliant!

But here's the interesting bit. I have looked at the this very aspect of molecular modelling (biologist speak) or quantum physics (geek speak) using atomic force microscopy. This technique allows the researcher to obtain a topographical image of the DNA molecule undergoing re-modelling; I can see a region of DNA 'open' or 'close' varying only by a single base change in the sequence. This very simple variation in DNA sequence therefore changes the molecular stoichiometry, which affects DNA folding and the accessibility of the gene to factors which promote gene transcription (I promise we'll get to that in the next blog entry). Furthermore, these topographical changes can be predicted using folding software, which helps inform biologists about the type of experiments we should be doing to further elucidate the mysteries of the DNA molecule. Important, I think you'll agree?

And finally, I remember that a Professor I know has published a useful book, which I think I'll have another look at now. To be continued....

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DNA unwound

DNA is fascinating. I have spent nearly twenty years getting inside this dynamic molecule, the basic component of human life, that controls hair colour and how long you will live and everything in between.

Every cell in the human body contains this miracle molecule. It's wound up inside the nucleus and can respond to our changing environment. For example, in work I have recently completed, I have been able to measure the rate of response of DNA to conditions mimicking inflammation in the wall of the peripheral blood vessels. Put simply, I created a laboratory model of atherosclerosis, which as you know is a thickening of the arteries, leading to heart attack and stroke. These experiments were important to do because they showed us how the DNA functions in cells from individual people with different DNA variations.

DNA is divided into functional regions, which we call genes. These genes contain naturally occurring variations, which makes us different from one another. Many of these variants are completely compatible with normal life; that is, the cell will grow and divide in the normal way. This is different from mutations such as those in cancerous cells, which cause aberrant cell proliferation and division.

In order for a region of DNA to respond to a signal from outside the cell, it must be in a relaxed or open state. A number of carrier or transport molecules including cytokines are responsible for presenting the stimulus to the open DNA molecule, in the correct functional position or gene. Once this has happened, the region of DNA closes, a bit like pushing a spring between your hands. In this closed the position, the function of the gene is turned off and no other molecules can interact with the DNA. Imagine a very fine orchestra with a very busy conductor making sure that nothing goes out of tune. All these processes happen without our conscious intervention, and that is what makes DNA fascinating.

Techniques developed in the laboratory by some very clever scientists have allowed us to visualise these processes. We can measure them and discern differences in them between different people, who have different gene variants. Thus, we can say that genetics can determine an individual's response to inflammation. But what do we do with this information. Well, in the not too distant future scientists would like to translate this research into the clinical setting so that family and hospital doctors may be able to look at our genetics when deciding on treatment.

Next time, RNA unplugged and proteins unmixed.

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Nature or nurture?

This is a well-travelled argument, but what does it mean in genetic terms? Who cares, I hear you ask? I do, and so should you.

We now know that many modern illnesses are multi-factorial complex diseases. That means that there is more than one cause of the condition, and often more than one treatment. Cancer and cardiovascular disease are good examples of this. For example, you might hear someone say 'they never smoked, always exercised, the heart attack came out of the blue'. We are told to eat five fresh fruit and veg a day, we are encouraged to know our numbers - blood pressure and cholesterol, we are implored to exercise for at least thirty minutes three times a week. But all of this will mean nothing if your genetics are against you. 


Cardiologists talk of risk stratification. This is a complicated formula which takes into account weight (body mass index), waist to hip ratio, blood pressure, cholesterol levels and family history, amongst other measurements. A family history of heart disease is a strong indicator of a genetic link, but often the science of genetics has not yet identified the culprit gene variant, or variants, or discovered the mechanism of the fault in causing disease.


So, in terms of genetics, the nature versus nurture argument is all about a person's individual DNA pattern interacting with one's environment, the individual lifestyle choices we all make. And both genetics and lifestyle contribute to the overall risk of disease; we just don't know yet what to do about this. But, this is a rapidly growing area of research which it is hoped will yield valuable insights into the risk of cardiovascular disease and cancer.


Fingers crossed.

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