Life in Dr Jim’s lab (part 1)

AS promised, I have finally found some time to start documenting some of the things we’re doing in my lab.

However, I’m starting small. Very small.

I’m going to tell you about some of the toys tools we use in the lab; no, not hammers and nails, and not even the fancy equipment you’ve seen on CSI*, rather, some of the simple and time saving technologies that make our lives easier.

So, we’re going to have some fun with superparamagnetic beads. That’s a mouthful! Superparaganetic beads are basically beads that are attracted to magnets, but which don’t become magnetic as a result +.

dynabeads
Caitlin (200) Nature Methods 2: 71 - 77

Our magnetic beads are tiny. In fact, each one is just 100 nm (nanometers), which is about 1/10,000th of a millimetre on a ruler (smaller than those in the image to the left, which are microparticles). These beads have a number of uses, but their main use is to bind to something you want to purify, and drag it out of a mixture of hundreds of other things that you don’t want. This mixture could be a biological sample, like blood, urine or liquefied poo; it could be a sample of contaminated food, or it could be an environmental sample, such as soil or seawater. In each case, there may be one thing you want to extract, a particular protein, a piece of DNA, or even a whole cell (human or harmful bacteria), but how do you get at it?

All you need is some basic knowledge of what the thing you’re after might like to bind to, some sort of molecular glue. Some proteins bind to other proteins, or DNA. For example, antibodies are used in your body to bind specifically to different types of foreign materials in your blood, a different antibody for each foreign material; they then alert your immune system. If you coat each bead with a particular antibody, say one that binds to a particular harmful bacterial cell like Salmonella, then you can add your beads to a mushed up sample of biological material, and use magnets to drag the beads (and the cells attached to the beads) away from the rest of the mush. You can then wash your beads a few times in a fresh solution and start your experiments.

Here is a video of some beads in action – though my sample is a salt solution, rather than poo!


My soundtrack (when it activates!) reminds me of my favourite film, ‘Sideways’.

Uses of magnetic beads:

  • Finding binding partners of your molecule of interest.
  • Deliberately pulling out a known molecule of interest from a mixed salad of other chemicals.
  • Pulling whole cells (human or harmful bacteria) out of a biological sample.
  • Having fun with magnetic beads.

* Whom, I should add, have managed to get DNA sequences out of a centrifuge – a piece of kit for spinning things to the bottom of a tube – in the time it takes to say, ‘Well, it seems to be our guy’s blood on the a paint sample matching a 1979 B-Body Dodge Charger’, which is clearly ridiculous**)

** Dodge didn’t make a B-Body Charger in 1979.

+ Remember your school physics, where you scraped an iron nail against a strong magnet, and the nail then becomes magnetic? If you went a step further, as I did, you would take you now magnetised nail into the woods with you, and when you got lost, you would find a clear and stagnant pool, upon which you would set your nail, atop a leaf, and float it on the water. The nail should then align itself North-South. Unfortunately, I could never remember which end of the nail point North, so it was a little fun, but pointless. The point being, your beads won’t just start floating towards any iron that happens to be near by.

Bad Science excerpt: The Doctor Will Sue You Now

bad-scienceBen Goldacre has released the infamous chapter that was missing from the original ‘trade’ paperback edition of his book, ‘Bad Science’. He recently posted the chapter on his Bad Science blog, under a Creative Commons license; this means ‘You are free to copy it, paste it, bake it, reprint it, read it aloud, as long as you don’t change it – including this bit – so that people know that they can find more ideas for free at www.badscience.net

I have reposted the article in full, but you can just as well read it on Ben’s blog, or hell, you could even go spend a few quid and buy his book!

This is an extract from
BAD SCIENCE by Ben Goldacre
Published by Harper Perennial 2009.

The Doctor Will Sue You Now

This chapter did not appear in the original edition of this book, because for fifteen months leading up to September 2008 the vitamin-pill entrepreneur Matthias Rath was suing me personally, and the Guardian, for libel. This strategy brought only mixed success. For all that nutritionists may fantasise in public that any critic is somehow a pawn of big pharma, in private they would do well to remember that, like many my age who work in the public sector, I don’t own a flat. The Guardian generously paid for the lawyers, and in September 2008 Rath dropped his case, which had cost in excess of £500,000 to defend. Rath has paid £220,000 already, and the rest will hopefully follow.

Continue reading “Bad Science excerpt: The Doctor Will Sue You Now”

Writing time…

So the university has afforded me some free time for the next five days, which gives me the perfect opportunity to get caught up on some of the science blogging I’ve been planning. In the next few days I will be posting some pictures and video that fall into the broad category, ‘Life in the lab’. In this I will be discussing topics, in no particular order, such as:

‘I’m just running a gel…’, – what does this line, often used by lab scientists, actually mean?

‘Using biology as a scaffold for building nano-electronic circuits…’ – this is some of the research I am involved in.

‘Toy’s for science boys (and girls)…’ – Yes, there are geeky tool kits (I call them toys) that we use in molecular biology. Most people won’t know the point of using them, let alone that they exist; I’ll attempt to explain why they’re cool.

Finally, I will be doing a research blog on ‘Targeted antibiotics…’ – new approaches to make antibiotics more useful, and that take out the ‘bad’ bugs, but leave the ‘good’.

Bionic eye…

This is just the sort of grass-roots level innovation that has made science and technology great; interested people doing interesting things. This is a video by Canadian film maker Rob Spence and is from his ‘Eyeborg‘ project website.

You can keep apace with their current progress via their blog.

Amusing encounter…

When exiting a pub in Keswick (Lake District) at the weekend, I walked headlong into a blind man and his Alsatian guide dog who were heading into the pub. He laughed and apologised, then told me, “Sorry, I’m following the dog; he never misses a pub!”

Classic.

Welcome to Mental Indigestion….

Not sure how you’ve arrived here? I set up a DNS forward from my old ‘time to waste’ blog. You will find all the content from that blog in this blog. In fact, there is very little difference, other than that the name and domain of my blog now match.

I have every intention of up-scaling my coverage of science, which will be in bite-sized pieces to help prevent mental indigestion. So if anyone is suffering with brain biliousness and needs an intellectual Alka-Seltzer, then you’ve come to the right place.

Word.

The strength of great apes…

The next time you’re down the pub, engaging your favourite Chimpanzee in an arm wrestle, I want you to reflect on a few things (besides the absurdity of wrestling an Ape).

As you take up the strain, know that the fine-tuned positioning and slow, steady building of muscle force you exert is due to the greater amount of grey matter that you posses in your spinal cord; motor neuron nerves cells that connect to muscle fibres and regulate muscle movement. The huge surplus of motor neurons you possess allows you to engage smaller portions of your muscles at any given time. A Chimpanzee, by comparison, has fewer motor neurons, thus each neuron triggers a greater number of muscle fibres, resulting in a greater proportion of muscle activation.

Reflect on how this finely tuned, incremental strength allows you to engage in tensing your muscle for a longer period. It is this fine motor control that allows you to do delicate tasks, like be victorious on the Nintendo Wii or replace the RAM in your laptop, and you know that if the RAM chip stubbornly refuses to slot back into place, you can gently exert greater and greater precise force until it does.

Finally, as the arm wrestle begins in earnest, reflect on two last things: one, your brain limits the degree of your muscle activation in an attempt to prevent damage to the fine motor control components of your muscles; and two, a Chimpanzee has no such limitation. So as the Chimpanzee tears off your arm easily and beats you over the head with it, think to yourself that rather than engaging in an arm wrestle with a Chimp, which has four times your strength, try sitting at home playing your Nintendo Wii instead, the precise motions for which it seems we are supremely evolved.

Inspired by Alan Walker’s (Professor of Anthropology at Penn State) research article ‘The strength of Great Apes and the speed of Humans’; free to read in the recent issue of the journal Current Anthropology.

Like this article? Please consider submitting it to Open Lab 2009:

Open Lab 2009

Letter to The Guardian…

A little long, didn’t fly, but better luck next time.

[Guardian, Tuesday 31st April] Cherill Hicks article, ‘Not to be sneezed at’, gave a timely and largely useful revision of therapies available to hay fever sufferers, but tripped up by suggesting that research on homeopathic treatments was ‘encouraging’.

It is still the consensus in the scientific literature that homeopathy does not perform any better than placebo, an issue which has been addressed by a comprehensive study by Aijing Shang MD and colleagues at the University of Berne, Switzerland. The study, published in The Lancet (2005), compared 110 homeopathy trials with 110 conventional medicine trials, and found that conventional medicines work, with little evidence to say the same of homeopathic medicines.

The positive findings of a few placebo-controlled trials of homeopathic medicines are cherry picked from a mountain of contradictory results, and are generally found to result from combinations of methodological deficiencies and biased reporting. The ‘encouraging’ results for treatment of hay fever with Galphimia glauca arise from a series of studies by a single homeopathy research group, and have been given unwarranted kudos in homeopathy circles due to the publication of a meta-analysis, which is an analytical over-view of combined results from numerous methodologically similar studies.

However, the meta-analysis only consists of seven trials (included in the Lancet study by Dr Shang and colleagues), and all come from the same research group; indeed, the group leader was a co-author on the meta-analysis itself. There are insufficient data from independently reproduced studies to corroborate the positive findings for Galphimia glauca as a treatment for hay fever, thus its status as a recommendable therapy is dubious.

Good idea….

A technique to ensure/encourage patient compliance was recently described on the Freakonomics blog. In the example they described a device that could be used to detect the metabolites (breakdown products) of TB medication in urine.  It was developed by Jose Gomez-Marquez and colleagues at MIT’s ‘Innovations in International Health’ programme; a more detailed discussion of the history behind its development can be found at MobileActive.org. Biosensors such as these are these are nothing new of course, but it is the potential application that is interesting. Essentially it is a device that encodes a pattern, or series of numbers or code, that can only be revealed by urine from a patient who has been taking their medication. This pattern of number could be their entry to a ‘lottery’ or some other economically-driven, and presumably ethical, contest.

It is certainly an interesting idea and can be derivatised for numerous treatments that require patient compliance. As the Freakonomics blog describes, it is an excellent fusion of economics and science, using the tangible prospect of economic gain to encourage patients to address the rather esoteric long-term treatment of slow-healing bacterial infections such as TB.

It is one of a number of tactics, along with new drugs that reduce treatment time, that could be brought to bear in the light of the rather sombre report ‘Global Tuberculosis Control 2009‘ commissioned by WHO, which is discussed in an editorial in The Lancet (4th April edition).