mindlace

Today I discovered that this gent and his lab have just won the Descartes prize for their study of mitochondria. It is quite appealing to see somone winning a major prize for this sort of microbiological work. It is also good to see that eccentricities of dress and character are not barriers to achieving precisely the kind of position – award winning director of a research lab – that I personally aspire to. It is also intriguing to hear that he opted to move to Finland for a more friendly research climate; Finland seems to have quite a lot going for it.

Now that I am a matriculated student, I would like to articulate the purpose of this educational enterprise. The world has recently begun to systemically view microbes as factories. On an individual basis bacteria and other microbes are already widely used for many industrial and research tasks, from providing surfactants and enzymes for detergent to being a vector to express a protein. These applications all follow a similar approach, where you grow a large population of free-living bacteria then lyse the batch and use some extraction technique to get the molecule of interest.

I suspect that when we more fully understand quorum sensing and other forms of microbial signalling in heterogeneous environments it will be possible to cultivate macroatomic biofilm-based structures that are useful as human artefacts.

I believe that the capacity to construct our artefactual space out of living organisms will finally allow all humans to posses the means to provide for their material needs; at a bare minimum, structures and devices built of living things have many admirable properties, not the least of which being complete recyclability.

I just finished reading “Gene Order and Dynamic Domains” (from whence the image is taken). It reminded me again how different evolved solutions are from designed ones.

In eukaryotes, DNA is bound into various higher order structures. They start by being bound into nucleosomes and from there form a variety of more complicated structures. Trivially, this helps the DNA fit into the nucleus, but probably more significantly, DNA that is wrapped up cannot be transcribed into pre-mRNA on its way to becoming a protein. So arguably the more important function of nuclear organization of DNA is a regulatory function. It turns out that even when “untangled” in interphase, the non-dividing portion of a cell’s life cycle, chromosomes keep themselves more or less together in “chromosome territories”. While they aren’t in the highly compact condensed form you’re probably used to seeing them in, they do have a geometry, and in that shape the gene-coding reigons are preferentially oriented toward the outside of the chromosome territory.

While this favourable geometry is encouraged by various dna-binding molecules, the amazing thing is that the sequence of nucleotides is important. It’s hard for me to come up with any appropriate analogy in human terms because we don’t do things this way – for example, while the very first portions of a computer’s hard drive are important, for the most part the sequence of bits on a hard drive are irrelevant to its function.

The way this mingles message and structure is a common motif in living things, almost everything does double or triple duty- nucleotides code for proteins and provide scaffolding to place the appropriate nucleotides in a transcription-friendly orientation, RNA acts as messenger, enzyme and censor.

It may just be an artifact of my interpretative framework, but it seems clear to me that the human mind does not work towards design solutions like this. We tend to think “house”, and then think of what we can make it out of. Even in a “materials first” case, we tend to take into account a certain small number of the properties of the material in question and find a novel utilisation for those properties.

Furthermore, while I don’t personally know any non-human intelligent designers, this property of our design approach seems to be close to the heart of what we call intelligence, for it is this ability to only consider specific properties and to design from a sort of “top down” perspective that gives us the ability to do and make things that seem to deviate from the capacity of the living world – from setting our bones when they break to designing next year’s automobile.

In “A Structural Analysis of Eukaryotic Membrane Evolution“, the authors argue that the Nuclear Pore Complex, which is a “gatekeeper molecule” that controls what proteins can make it into and out of the nucleus of a eukaryote, may have originally been a membrane folding protein. Folded membranes are very important to Eukaryotes, who use them for practically all their organelles. While prokaryotes largely do not posess organelles, a folded interior membrane is still important for cyanobacteria, who use them to boost the surface area capable of undergoing photosynthesis. This provides an insight into the evolution of the Nuclear Pore Complex, a molecular structure that is extraordinarily complex and completely unnecessary for prokaryotes. The take-home lesson is exaptation is a major driver of evolution, and one that helps explain seemingly miraculous leaps in organismal design.

At least 16 organisms from a diverse array of evolutionary lineages deviate from nature’s standard code in the amino acid “meaning” they assign to specific codons.
evolution encoded, sidebar

I had no idea there was deviance in the amino acid encoding – that’s extraordinary! The larger article gives a wonderful overview of how the basic encoding techniques of life – how amino acids are made from dna – help positive mutations to occur and help mask negative mutations. Very interesting.

In other news, the TCA cycle is as fascinating as always, though I’m disappointed that the text I’m reading now doesn’t point out that it’s driven backwards in some obligate anaerobes in order to synthesize the molecules that are intermediaries of the process.

I was interested to learn that the phosphorylation of glucose at the beginning of the oxidative process renders it incapable of leaving the cell membrane; I was also surprised to learn that chloroplasts are impermeable to NADPH and ATP.

The cover story for last week’s nature is all about fusing membranes. There are a number of circumstances where membrane fusion occurs; in the article they mostly talk about lipid-coated viruses. In lipid coated viruses, they essentially have a membrane like a regular cell. (This is one of three major coating strategies)

Although this is the first time I’ve encountered the subject, this has apparently been the matter of some heavy research as of late. In 2002 they showed what was going on in the two bilayer membranes during fusion, but this didn’t elucidate what was driving the process.

When a virus encounters a cell it has to bond to the cell and somehow get its DNA or RNA into the cell; in membrane viruses they achieve this by two sorts of fusion proteins, lyrically named “class I” and “class II” fusion proteins. The article is mostly about a recent articulation of the behaviour of class I fusion proteins, which were thought to perhaps use a markedly different strategy than class II fusion proteins. It turns out that they are fairly similar, but do not rely on the acidic pH that class II’s do; what this means is class I proteins attach to external membranes, whereas class II proteins are deployed once a cell has “eaten” the virus and has contained it in an inner vesicle (called an endosome).

To me, the interesting thing is that these membrane fusions are very mechanical; they are a result of the conformational properties of the fusion proteins, and do not require the input of any energy bearing molecules.

Basically, a virus is studded with type II fusion proteins, thought to be arrayed in rings, folded in a “closed” state. When the virus gets close to a cell, the fusion proteins’ tips are attracted to and latch on to receptors (other little stickey-outey proteins)

I was always kind of confused about receptors; why do cells stick all of these hand-holds on the outside of their membrane if it just makes them virus targets? What I learned is that the cell has no real choice; in order for proteins to cross the membrane at all, they have to have little “transfer” bits that stick in the membrane and help the protein get across. Then the active bit gets sheared off by other membrane molecules, and as a result the transfer bit sticks around for a while, a little nubby docking station for a virus to take advantage of.
The other thing that happens is that the protein is *not* sheared off, and is actually used to help the cell stick to other cells – these are called cell adhesion molecules (CAMS).
I don’t actually know if CAMs or these transfer stubs are viral “receptors” but I think it illustrates the broader point that the cell has to stick lots of handy molecules into its membrane during its normal operations. on the cell membrane’s surface. This binding causes the protein to change into an extended shape that sticks hydrophobic “hooks” into the target membrane. This attachment frees up energy in the molecule and causes it to start to refold, dragging the two membranes closer to each other until eventually in a little area they start to merge (when brought close enough together, lipid bilayers want to merge kind of like soap-bubbles are wont to.) So now you can imagine two balloons squished together, forming a circle at their point of attachment; the fusion proteins are now little hair-pins around the circumfrence. At this stage the folding proteins settle into their most stable state (lower energy than the “ready to fire” conformation they had before this all started) and the membranes are fully bound to each other.

At this point, unless there’s something else keeping the membranes structurally distinct, they merge completely together; the littler membrane sack just flattening out into the larger membrane; this is a happy thing for the virus as it squirts the dna and “attack” proteins right into the target cell. All of this has happened without any input of energy; it’s like these molecules were spring loaded. Needless to say the folding proteins themselves are insanely complicated, and the folding involved rather intricate.

Now, all of this makes membrane fusion molecules sound and awful lot like weapons of cell destruction-related program activities, but these are some dual-use molecules; it seems that neurotransmitter laden synaptic vesicles are used to transmit neurotransmitters across neurons. This sounds like an interesting issue, to me; because in this case there’s not only a clear need for vesicle formation and membrane fusion to happen rapidly but also repeatedly, so it would lead me to wonder whether or not the membrane fusion molecules involved (evidently having the clever nickname of SNARE) are as one-way as the fusion molecules deployed by viruses.

Heat vents create heat gradients, which create chemical gradients.
Being able to stay at a particular place in those gradients
conferred selective advantage. Therefore microbes developed
a way to react to incoming infrared photons; the energy of heat
was information; it was “seen”.

Eventually some of these bacteria through tides or tectonics
find themselves in shallow water; suddenly there is a new, vivid source of photons.
The same molecules used to harvest photons for information are getting enough news to eat.
The information was a source of energy.

Bacteria and archaea gain energy by creating an electrical potential
gradient by pushing protons across their membrane; from this gradient all energy-bearing
molecules are formed. This energy drives metabolic processes that result in molecules that are,
to various extents and by differing methods, assisted across the membrane. Bacteria of the same
and differing strains respond to the presence of these molecules.

Neurons, though their prime energy-generating membrane is in an internal organelle, use electrical
potential across their membranes to transduct a signal to a synaptic gap, where molecules are
transported across the membrane with a high degree of specificity.

How much do these flows of potential and molecule have to do with each other? Gerald Edelman in [A Universe of Consciousness][a] suggests a mechanism for identifying functional clusters in neurons; similar techniques should be applicable to populations of microbes.

[a]: http://www.amazon.com/exec/obidos/ASIN/0465013775/mindlace-2

The other day I came across some nicely artistic photos of decaying animals. They remind me how interested I am in the process of decay, which made me think about what a decay-centered biology career would be like, which made me think of the nine billion biology careers I could have, which made me come back to the conclusion that I should explore biology as broadly as possible during my undergraduate days, in lieu of starting from the presumption that I want to be working with biofilms.

In Adam’s Curse, Bryan Sykes makes the argument that theY chromosome has ~150k years left, at best. Unfortunately, the book isn’t available in the states yet.

In an exhaustive review of temperature-indicating phenomena, Jones P and Michael M find that The last 20 years have been hotter than the last 1800. Jones says “The climate sceptics are flogging a dead horse.”

Doonesbury suggests a pre-emptive recall petition.

In Bacteria as Multicellular Organisms they discuss terminal transposon mutations induced by environmental conditions that, while preventing the mutated bacteria from reproducing, permit its colleagues to do so.

My stay here may be somewhat short lived as I’ve found Syncato, a weblogging tool so utterly drenched in acronyms it can’t help but be the l33t thing to do.

It uses Sleepycat’s XML database and a plethora of additional open-source xml manipulation API tools to build – in python (woot!) a REST based system for working with xml fragments.

This, if I manage to combine it with my existing approach of using subversion to manage my longer documents, might bring about a sort of “semantic web for one” toolkit, where you can describe yourself and what you’re working on, believe in, or what have you using as much or as little semantic markup as you want.

As tools spread out there capable of using xpath for querying, the whole internet becomes as queryable as your own database. Eventually this will be common way for us non-business types to engage in spontaneous community; when a critical mass of people expressing similar semantics arise, so to will their ability to cohere for whatever purpose (or lack thereof) their semantic commonalities suggest. Tools like Technorati are already doing this with what little semantic markup blogs provide today; and technorati itself is already providing a REST-style API.

Let the business world stifle in their stew of stuffy standards and opaque encapsulation whilst the rest of us get by on tag soup and running consensus.

Anyway, so bacteria are opportunistic multicellular organisms, and that opportunity exists almost everywhere except the lab. Right now I’m curious about exactly how diverse is the set of exogenous polysaccharides bacteria and archaea produce to facilitate cohesion; are there, for example, bacteria that use xylan -based or N-acetylglucosamine based polysaccharides? If so, there’s a possibility that you could make woody or chitinous biofilm cultures.

Also, maybe precise placement of different strains of bacteria could get you more interesting control over the constitution of your resultant biofilm; deposition of bacteria from live culture using something like an inkjet could be a way to cheaply get that sort of distribution.

Microencapsulation is pretty doable these days as well; perhaps encapsulating either sporing or otherwise suspended collections of bacteria in materials and then “printing” them amongst populations of bacteria that produce exogenous reducing enzymes for that material could allow you to get a time-delay effect in the production of some aspect of your final desired structure.