Mental Indigestion

by Jim Caryl

Month: April, 2009

Wordle of the month…

See what I’ve been writing about this month in one typographitastic image, courtesy of Wordle:

April

April 2009 Wordle

Re-awakening ancestral genes…

Research bloggingHUMANS, as we know, are the product of tens of thousands of genes, but hidden elsewhere in your DNA are genes that are no longer functional; these vestigial genes are known as pseudogenes, and they are ancestral remnants from an earlier point in our evolution. In many cases they are simply inactivated duplicates of a current functional gene. In other cases they are genes that have been cut out, reversed and stitched back in; in this position, some believe they may act to regulate the correctly oriented ‘functional’ version of the gene. Alternatively, they may be ancestral genes encoding functions that have become inactive beacuse they are ultimately not necessary for survival. Now, what if we could turn on one of these ancestral genes? One that could actually help protect us from a modern day infection?

In the recent edition of PLoS Biology is an interesting study that describes the re-activation of just such a dormant human pseudogene, retrocyclin, and its potential use as a defensive barrier against infection with HIV-1 (a strain of the Human Immunodeficiency Virus that causes AIDS). Retrocyclin is theta-defensin, which are naturally produced, circular chains of 18 amino acids (a peptide). I have previously research blogged about the application of other such antimicrobial peptides.

Active, functional theta-defensins have only so far been identified in the old world monkeys: the Rhesus Macaque and Olive Baboon; in Humans and other primates, they exist as pseudogenes. At some point in evolutionary history, our ancestors started inheriting a genetic mutation, all be it one that exists at 100%. The Human version of the gene, retrocyclin, is inactive in Humans because of a premature ‘stop’ signal, which makes the cell abandon the production of the peptide too early.

Retrocyclin can be synthesised chemically in a lab, and in this manner that the authors of this paper (from laboratories at the University of Central Florida and UCLA) have previously shown that it is capable of inactivating HIV-1, thereby preventing its entry into cells; in fact, they have also shown that it can similarly prevent entry of Herpes Simplex Virus type I (responsible for coldsores) and type II (responsible for genital warts).

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Basic research…

[ratings]

TODAY ‘The Scientist’ reported that the UK government is going to bail out biotech, investing £750 million ($1.1 billion) to bolster this and other ailing commercial science and technology sectors. This isn’t a bad thing, per se, but at what cost?

Well perhaps it comes at the cost of ‘basic research’:

Government funding for basic research, however, will receive no additional funds. Buried deep on page 130 of the new budget, the government called on the public research councils, including the MRC and the Biotechnology and Biological Sciences Research Council, to reallocate £106 million ($154 million) of their pre-existing budgets to support key areas with predicted economic potential — a plan which leaves some science lobby groups less than happy.

They’re going to move money around, rather than putting more into the areas of basic scientific research. In contrast, the US government’s economic stimulus package has fed money into the National Institute of Health (NIH) and National Science Foundation (NSF), between whom most of my US scientist friends are funded in their basic scientific research.

But what do we mean by ‘basic scientific research’? The term, synonymous with fundamental or pure research, is first and foremost a quest for knowledge; it has no specific end goal or commercialisation, i.e. a practical application cannot be envisaged. We might also consider research that may yield a commercial application after 10 -50 years to be basic research too (I put my own current technologies work in this bracket). Applied research, in contrast, is work that is aimed directly at a specific commercial end, such as development of a particular drug.

So what’s the problem in the UK, why are we bothered?

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Open mindedness…

THERE is a video floating around the interweb that has proven very popular since its release; it’s called ‘Open-mindedness‘, by a chap called Doug (aka Qualia Soup).

I have forwarded this to numerous friends whom I felt may benefit from this perspective, and also to people who find themselves on the receiving end of being called ‘close minded’, essentially for banal things such as not believing in ghosts. However, in several cases now, it has been pointed out that the video has some flaws. These flaws are not so much to do with the content, but are more to do with the speed at which these potentially new concepts and argument are played out. As such, there is a risk that they may miss their mark in precisely those people who would most benefit.

For my own reference, and for some of the people who I know haven’t quite gleaned what the video is getting at, I’ve written a  para-phrased version that can be read and digested at the reader’s leisure; basically, I’m spelling it out. The core material and structure is taken directly from the video:

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Dressing up biology like a circuit board…

WHAT’S this then?

This is an electron-micrograph (a picture taken through an electron microscope), taken at 56,000x magnification. It also happens to have been taken by me. What you’re looking at is a filament of protein, called an ‘amyloid fibril’.

Nanowire filament

The straight fibril that runs from the centre of the picture to the the bottom-right, is 0.5 microns in length (about quarter of the length of an E. coli cell, or 1/2000 of a millimetre). Each of those dots is a sphere of gold that is 5 nanometres in width.

To understand something about amyloid, we need to do some very basic revision on what proteins are:

  • Some proteins make up the structure of your body’s tissues;
  • some act as cellular emails, enabling cells to talk to each other; and,
  • some are also known as enzymes, and perform almost all of the millions of biochemical reactions that result in you.

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The dead zone…

rb2IMAGINE that you’re walking along a path in the middle of a prairie, minding your own business. As you’re walking, you find yourself getting out of breath; you find you’re unable to exert yourself as you can’t seem to breath fast enough. Pretty soon you start becoming slovenly, slow moving, dulled; there’s something wrong with the air, there’s not enough oxygen; you’re in the ‘dead zone‘. You try to move away from where you are, but you don’t know where the bad air started. Before long, it’s too late.

A similar experience may happen to deep ocean fish. They need oxygen too, they just manage to get it from the water, but there’s a problem. A report in the April 17th edition of Science, by Peter Brewer and Edward Peltzer (Monterey Bay Aquarium Research Institute, Moss Landing) describes how ‘Ocean “dead zones” [defined as regions where normal respiration is greatly limited and the expenditure of effort is physiologically constrained], devoid of aerobic life, are likely to grow as carbon dioxide concentrations rise.’ In order to understand what their report is about, we need a little background.

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To whom are they selling…?

IN the past few years I have found myself on the receiving end of some fairly bizarre advertising campaigns from large biotech companies.

First there was MWG Biotech (as they were called at the time), who make short stretches of single-stranded DNA called oligonucleotides, which many of us use in our experiments. They decided to market these using cartoon characters, the chief of whom was ‘Olly Oligo”. This was the first time I asked myself, ‘who the hell are they aiming this at?’

Then we were assaulted with the extremely kitch ‘PCR Song‘ from Bio-Rad. Thanks for this guys, it took weeks to try and forget it.

PCR song

Bio-Rad's PCR Song

Then came Eppendorf’s ‘It’s called epMotion‘ music video for a robotic liquid handling station; a deliberately tongue-in-cheek boy-band styled affair, also available as a ring tone. I wasn’t swayed.

Eppendorf's epMotion boys

Eppendorf's epMotion boys

The most recent shockers, inciting this post, are from the Biotech giant Roche, who are marketing a means of monitoring cell cultures using electrical impedance measurements, xCELLigence. However, they’ve gone for a more obvious tack. They’ve done a rock video.

Roche's exCELLigence rock

Roche's exCELLigence rock

Actually, they loved it so much, they did a second rock video. Why do just one when you can have two videos for twice the price?

I’m actually now speechless.

Bio suit…

HOW human do you think you are?

100% ?

90% ?

Well, let’s play a numbers game: in terms of cell numbers, you have in the order of a trillion cells in your body, though this value varies greatly between people and is constantly changing within each of us. However, you have some ten times this number of bacterial cells within (and on) your body 1. So at one level at least, you are only 10% human.

Of course, bacterial cells are quite a bit smaller than your cells, so there’s room for the both of you, in you.

bladder lactobacillus mouth1_scale_final
Images of human epithelial (tissue surface) cells coated with bacteria.

In terms of genes, the instructions that make you you, humans have about 30,000. Again, there are in the order of a hundred times this number of bacterial genes operating within and on your body 2. So at another level you are only 1% human.

Don’t worry though, of course you’re 100% human. Instead, we need to consider the extent of what being human actually is. Being human comes part and parcel with being a super-organism. We live in a symbiotic relationship with hundreds of different species of bacteria, without which we could not survive. Think of them as an invisible extension of your body’s innate defences, occupying every external surface, your skin, your gut, your eyes, ear, nose, and various other orifices.

There is mounting evidence to suggest that they influence our development; our physiology; our nutrition and metabolism; and immunity, where they play an important role from birth in educating our immune systems. They are your interactive suit of armour, both part of the environment and part of you. These communities of bacteria are referred to as the microbiome, and they are being investigated as part of the Human Microbiome Project, an effort by many research labs coordinated by the National Institute of Health.

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Targeting antibiotics…

rb1INHERITANCE, the process by which some of your parents DNA is repackaged in the agreeable form of you, can be described as ‘vertical gene transfer’, i.e. the passage of information down a lineage. However, this is not the only means by which DNA information can travel.

I once spent six years conducting research into the mechanisms by which resistance to antibiotics can be spread within, and between, bacterial species. Much of this focussed on horizontal gene transfer (HGT), specifically the transfer between bacteria of DNA packages called ‘plasmids’, which can contain a full set of instructions on how to resist an antibiotic. Unlike inheritance, HGT is more akin to you reaching out and placing your hand on your cousin and acquiring their ginger hair, or nose shape.

This is of course a very serious issue, in fact it has never been more serious. The subject of HGT is a key topic in many aspects of biological sciences, and I’ve blogged about some of the interesting aspects of such DNA information transfer before.

In the past 10 years or so, an oft’ discussed topic of conversation at the scientific conferences I’ve attended has been the development of targeted antimicrobials. This is a move towards being able to ‘take-out’ (in the mafia sense) those specific bacterial species that are causing a particular infection/disease, but without providing a selective pressure to develop resistance to the drug on this, and neighbouring, bacterial species.

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Amalgam fillings are safe…

AMALGAM, a compound of mercury with another metal, has been used for fillings for 200 years. A ScienceDaily news article says, ‘Amalgam fillings are safe, but sceptics still claim controversy’.

Speaking at the 87th General Session of the International Association for Dental Research in Miami, Dr Rod Mackert, of the Medical College of Georgia, points out that someone would need 265 – 310 amalgam fillings before even slight symptoms of mercury toxicity could be felt. The reason being that when mercury is mixed with the other metals used in fillings (silver, tin and copper), the compound produced contains no free mercury. A poison is only a poison when it is at the right dose; a fact that has been appreciated for hundreds of years. You may absorb only 1 micrograms (1/1millionth of a gram) of mercury a day from a mouthful of fillings, yet consume around 6 micrograms from food, water and air, according to the US Environmental Protection Agency.

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