Mental Indigestion

by Jim Caryl

The ‘negatome’ – a database of negative information…

Research bloggingWE researchers often joke that no-one ever publishes negative results, but that doesn’t mean to say that negative results aren’t extremely useful. On one level, knowledge of such negative results can prevent you repeating the same mistakes that countless other researchers, in other labs, have undoubtedly made over the years. On the other hand, they can provide a valuable dataset with which to generate new and useful information. One such example is the ‘Negatome Database‘, which has been reported by Smialowski et al.1 in Nucleic Acids Research advance access (November 17, 2009).

The Negatome is a collection of protein and domain (functional units of proteins) pairs that are unlikely to be engaged in direct physical interactions. But why on Earth would we want to know about proteins that don’t interact with each other; in fact, why do we need to know about proteins that interact at all?

Macromolecular machineResearchers recognize that that a cell doesn’t function purely by the action of individual proteins, but instead by large macromolecular complexes mediated by many interacting proteins.  The image to the left indicates an example macromolecular ‘machine’, in this case those involved in signal processing at the neuronal synapses (and which are likely to be working quite hard right now!).

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I WAS in London last weekend (pics) meeting some wonderful people. One topic of conversation that came up late one evening was spirituality. It’s something that I have, in the past, had a lot to speak about. However, often pre-conceived notions of what spirituality really means (and we are well into in the realms of semantics here) hinder some discussion. This wasn’t the case the other day; as cursory as the discussion was, spirituality was not viewed as a skeptically-negative concept, but we were all way too tired, and the safe side of sober, for that discussion to last.

I’m re-posting an old post, written when I had something to say about the matter.


Post, of the same name, re-posted from an earlier incarnation of this blog:

AMAZEMENT still strikes at our primitive emotions. When we are left in bewildered awe at a spectacle or new insight, it tugs at us in a manner that a reasoned scientific account can do no justice. It is, in many respects, a “religious” experience, but the word “religious” is bandied around in place of a slew of terms that could be used.

Such experiences are spiritual, being of matter (the brain still being a material object), yet insubstantial and deeply emotive. Whether it is some perception of a deity, or a new dimension of worldly understanding provided by science, these experiences are linked in their spiritual nature. In fact, I am with Carl Sagan in my belief that science is a profound source of spirituality.

In talking about spirituality, there is no implication of talking about religion. Spirituality is a sense of meaning (or purpose) and unity, but it does not have to be divinely inspired; it should not be confused with mysticism, which is concerned with magic, the occult and supernatural. The scientific journal Nature defines spirituality it as “An inner sense of something greater than oneself. Recognition of a meaning to existence that transcends one’s immediate circumstances”. It’s a good word, and one that we ought to take back, releasing it from its pre-scientific context.

Nature and the universe certainly put us in our place with the realisation that the atoms that make up your body are billions of years old, they’ve made many other things in their existence, and will continue to do so long after we’re gone; we are simply borrowing them for a while. Scientists, and readers of science, have a lot to be spiritual about. We have a particular impulse to understand the world around us. It is a great injustice to ignore the natural world in favour of an inferior and artificial facsimile in the form of the supernatural. Why ignore what is in front of your eyes, from the sub-atomic to the cosmos, and instead make it up?

Science doesn’t have all the answers, but it has more than any faith can offer me. Science has so many more questions that it will answer, whereas most faiths have said everything they have to say. Fortunately, as a rational human being, and a scientist, I don’t need anyone to agree with me to be comfortable in my reasoning. If a million scientists decided to recant on DNA being the basis of genetic inheritance, unlikely as that is, it would mean nothing. DNA would still continue to be the basis of genetic inheritance unless they had hard evidence to the contrary. It is this facility than enables freethinking, rational people to be truly uninhibited and unprejudiced.

So why is spirituality important? Science can, in a practical sense, only really deal with the material; though this “material” may extend well below the size of an atom, or may be as intangible as love or trust. We still inhabit physiologically stone-age bodies with minds hard-wired for day-to-day problem-solving, strategic planning and interacting with the physical world that our ancestors could see, hear, touch, smell and taste. Yet we managed to arrive at this state in the absence of both writing and mathematics. Most of what we’ve achieved since then has been achieved by co-opting these more primitive thought processes (the original “transferable skill” set) and applying them in a new direction: complex reasoning and abstract theoretical modelling, applied to science and mathematics.

It is no surprise, therefore, that much of what we have learned in science is difficult to process, especially when they are beyond the resolutive power our innate senses; we need things to have defined boundaries and exist at the right scale. We know there is a sense of change; that processes are shaping life, the planet and the universe around us. We are part of something shared, much greater than ourselves, and every time science offers a new awesome insight into this, we find a connection with our spirituality.

Windshield splatter analysis…

rb1A few years ago I took part in an RSPB survey called the Big Bug Count, which sought to quantitate what had hitherto been anecdotal accounts that the number of insect splats on car windscreens had decreased in recent years. Essentially it was a sticky pad of define area that was placed on the front registration plate of your car. Following a car journey (I drove the 20 miles from from Keswick to Windermere), the number of bugs splats were counted and the results submitted.

Some suggested that the dwindling insect splats may in fact be due to cars being more aerodynamic, and not the tin boxes of previous decades. However, even I had noticed that I was swallowing fewer bugs on my bike rides around Cumbria than my childhood years, but hardly scientifically rigorous data – I do after all scream with glee less now than I used to.

Unfortunately, because the ‘bug splat’ survey, as it became known, was the the first such study by the RSPB, they could draw no conclusions as to whether the insect population was dwindling (despite what some press articles claimed) until subsequent seasonal surveys, over multiple years, were performed.

Of course, what some of you may have noticed is that the RSBP doesn’t seem to have followed up with any further surveys – at least none that I’ve been able to find in 30 mins of googling and scouring their website. Shame, so we had a baseline, of sorts, against which nothing further has been measured.

But assessing species diversity is an important task, as I’m sure anyone can appreciate. Changes in biodiversity act as markers of climate change or pollution, and have knock on effects on the food chain, such as bird life.

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Stand up for research…

I’VE had a bit of an axe to grind recently about the government’s proposed policy on requiring such a large proportion of research funding to be allocated on the basis of economic and social impact. The University & College Union (UCU) is curently hosting a petition, signed against the statement that I’ve copied from their site below.

Sign it if you care to.

From the UCU’s website:

The latest proposal by the higher education funding councils is for 25% of the new Research Excellence Framework (REF) to be assessed according to ‘economic and social impact’. As academics, researchers and higher education professionals we believe that it is counter-productive to make funding for the best research conditional on its perceived economic and social benefits.

The REF proposals are founded on a lack of understanding of how knowledge advances. It is often difficult to predict which research will create the greatest practical impact. History shows us that in many instances it is curiosity-driven research that has led to major scientific and cultural advances. If implemented, these proposals risk undermining support for basic research across all disciplines and may well lead to an academic brain drain to countries such as the United States that continue to value fundamental research.

Universities must continue to be spaces in which the spirit of adventure thrives and where researchers enjoy academic freedom to push back the boundaries of knowledge in their disciplines.

We, therefore, call on the UK funding councils to withdraw the current REF proposals and to work with academics and researchers on creating a funding regime which supports and fosters basic research in our universities and colleges rather than discourages it.

[12,007 signatures at 11:43, 16 Nov 2009]

Sign the petition here.

Food for thought…

FINALLY, some lectures that don’t require a trip to London. Some big names are coming all the way up North, way up to the provinces, to give lectures as part of a celebration of 150 years of On the Origin of Species:

24th November 2009

2pm: Dr Gordon Chancellor
Charles Darwin, his life and his science
Dr Gordon Chancellor is from the UK Data Archive at the University of Essex. He is an Associate Editor of which hosts the largest online resource in the world relating to Charles Darwin.

2.45pm: Professor Steve Jones
Is human evolution over?
Professor Steve Jones is Professor of Genetics at University College London and is one of the best known contemporary popular writers on evolution. He is a television science presenter and writes a science column in the Daily Telegraph.

3.30 – 4pm: Interval

4pm: Professor Sydney Brenner
The Reconstruction of the Past: Reading the Human Genome
Professor Sydney Brenner opened the JIF building in 2007, now known as the Wellcome Trust Brenner building. Sydney was awarded the Nobel Prize for Physiology or Medicine in 2002 for his seminal work on discoveries of organ development and programmed cell death.

4.45pm: Professor Sir Alec Jeffreys
DNA fingerprinting and the turbulent genome
Professor Sir Alec Jeffreys is Royal Society Wolfson Professor at Leicester University. He discovered DNA fingerprinting 25 years ago. Among other important aspects of this method is that it allows identification of people by detecting variations in their genomes and has altered forensic science world wide.

5.30pm: Close

It’s going to be popular. Off to try and get a ticket, otherwise I’ll be sweating it out in a lecture teatre watching a live video feed instead.

Holes in the ice…

Research bloggingCRYOCONITE (‘ice dust’) holes are small pock-like depressions that are strewn over the surface of glaciers, looking much like a pristine snow drift after you’ve thrown a handful of gravel at it. Such melt-holes have been documented on glaciers at both poles, and on other glaciated regions such as Iceland, Greenland, Canada and the Himalayas. According to one account, at least, cryoconite holes  have been a bane to scientists working on the Greenland ice sheet, the holes being typically full of slushy ice, and big enough to step in by accident. However, cryoconite holes have been the subject of much debate in recent years; a debate centring on their role as contributors to glacial melting. Read the rest of this entry »

Bug eat bug…

This post was chosen as an Editor's Selection for ResearchBlogging.orgAS if it’s not hard enough at the bottom of the food chain, being cannibalised by your own bottom-dwelling compatriots must add insult to injury. The soil dwelling Gram-positive bacterium Bacillus subtilis is fully equipped to take appropriate action when faced with food shortages; a sub-population of cells initiate a process of dormancy by turning themselves into hardy, robust spores. In this form the bacteria are capable of enduring temporary, or prolonged, harsh environmental conditions.

However, this is not a process entered into without some careful deliberation. Sporulation, the act of forming a spore, is an energy intensive process that results in the formation of the essentially inactive spore, and the death of the ‘mother’ cell producing it. It comes as no surprise, therefore, to discover that B. subtilis has evolved a means of delaying sporulation as long as possible.

In an alternative strategy,  a sub-population have a genetic pre-disposition to become cannibals.

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Risk taking and audacity in science…

Research bloggingIn the October edition of Cell1, Amy Maxmen, a New York based science writer, discusses how tackling long-standing scientific problems (i.e. studies that have been prone to failure), or refuting dogma, are perceived to be a poor strategy for early-career researchers; and contends that perhaps they shouldn’t be.

One of the reasons for this is down to the policies of research grant committees.

A common complaint among researchers is that in order to be funded, they feel they must submit conservative grants filled with so much preliminary data that their predictions aren’t quite predictions any more. As Venter says, “The problem in [grant] study sections is the philosophy of proposals being reviewed as contracts instead of ideas.”

My own thoughts are that sometimes the amount of preliminary data required in a grant submission is so great that you’re half way to addressing the research goals at the first base, but only at the cost of the remnants of the last grant, which were used to finance the preliminary studies for the next. It’s as if the research councils are looking for a sure thing, a guarantee of success.

This is not how science should work.

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Lateral thinking…

[Promoted from my Posterous ‘Overflow‘ blog…]

LATELY I have been wresting with a particular problem in the lab. I have been trying to put a rather complex DNA molecule down on a gold surface with the aim of having it perform the same chemistry on a surface as it does in solution.

Generally, when putting DNA down on a gold surface, we synthesise our DNA with a particular chemical modification, a thiol, on one end of the DNA strand. A thiol is essentially a sulphur atom, usually together with a hydrogen (-SH), and sulphur forms a strong bond with gold, so this is we want.

Unfortunately, we live in a very oxidizing world (basically, everything rusts), so my thiol gets oxidized to a rather less useful S=O. There are numerous other atoms that can reduce my thiol too, such as other thiols, or metals such as magnesium, zinc, copper etc.

This isn’t generally a problem as an oxidized thiol can be reduced back to -SH, making it ready to react with my gold surface.

Only, it turns out that my DNA adheres to the gold at too great a density. Like a mosh pit at a concert, the poor blighters are unable to move, and this results in them being unable to perform the particular reaction that they normally manage when not constrained.

So I modify my approach and use another layer between the gold and the DNA. This layer can be used to dictate how much of the gold surface is actually available to be bound. The chemistry is quite complicated, with several steps, all of which degrade quite rapidly, so it has me running around to make sure I get all the steps completed in time.

First a layer of long floppy carbon chains go down on the gold, and the ends of these molecules are reacted with another chemical that makes them able to react with yet another chemical, this latter chemical being capable of reacting with a thiol. Phew.

I have spent more time than I care to mention trying to get this approach up and running, all the while having to deal with the fiddly, slow and rather cumbersome thiol-based chemistry, which has a propensity to rust.

Then it occurs to me. The only reason I was using a thiol on my DNA in the first place was to stick my DNA directly to a gold surface. As I’ve already determined that we can’t do this (too dense), I really don’t know why I’ve spent time running around testing numerous crosslinking agents that can link the surface to my thiol-DNA.

Time to ditch the thiol and use something that connects DIRECTLY to the first layer of floppy carbon chains.


Apologies for my absenteeism this week, I have been busy researching some family history for an upcoming post, which I hope to finish soon. If you’re looking for some light Sunday reading however, please consider a selection of my other posts:

Fallacies of logic – how logic is abused to achieve nefarious and intellectually dishonest ends.

Bio-suit – how human do you think you are? An essay about the human microbiome, the zoo of organisms that live on us, and in us – without which we wouldn’t be here.

The strength of great apes – describing the folly of engaging in an arm-wrestle with a Chimpanzee in the pub.

A cure in the toxin – describes the early use of bacterial infection to treat some forms of cancer.

…and finally, a book recommendation, ‘Three cups of tea‘.