Science lol

While I eventually will get around to finishing the next in my series on birds and genomes, I just wanted to comment on something retrospectively funny. Right now, I'm rereading Endless Forms Most Beautiful (Amazon/Chapters) by Sean Carroll, and one of the comments about hominin evolution was that humans (homo sapiens sapiens) and neanderthals (homo neanderthalensis or, presciently, homo sapiens neanderthalensis) did not mate together.¹ The actual study itself was sequencing the complete mitochondrial genome, which upon analysis demonstrated that it was grouped outside of known human mitochondrial DNA and thus suggesting that neanderthals made no genetic contribution to our lineage. However, I remember reading somwhere (John Hawk's blog I think) that just because neanderthal mitochondrial DNA didn't survive to modern day, it wasn't conclusive evidence that neanderthals did not contribute to our somatic genome. And, ironically enough, the same group that lead the mitochondrial project also sequenced the neanderthal genome a couple years later and found that neanderthals did contribute to our genome afterall!^2,3 Et voila, science in practice!

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1. Green RE et al. 2008. A Complete Neandertal Mitochondrial Genome Sequence Determined by High-Throughput Sequencing. Cell. 134(3):416-426.

2. Green RE et al. 2010. A Draft Sequence of the Neanderthal Genome. Science. 328:710-722.

3. Only applies to H. sapiens sapiens whose ancestors left Africa.

Of birds and genomes

One of the things I've been doing recently is marinating myself in the literature on avian genomes. My interest in it was sparked by an offhand conversation with my boss about birds and their small genomes, and so this post is going to be the first in a series that will be part historical, part summary, and part speculative, so as to clarify my understanding about the issue. I hope I don't foul it up!

The fact that avian genomes are, as a general characteristic of their clade, much smaller than the average vertebrate genome has been known for decades.^[1] Many people have tried to explain this size discrepancy with both adaptive and non-adaptive arguments, with some ideas perhaps more convincing than others in my limited understanding. But whatever the explanation, the small nature of the avian genome likely had a hand in derived adaptations in avian immunity, specifically B cell biology. B cells were discovered in the 1950's when researchers (among them Max Cooper who now plays with lampreys) removed an organ called the "bursa of Fabricius" from baby chickens. These bursa-less chickens demonstrated a loss of antibodies, which had two big implications in that: 1) cells in the bursa probably had a role in making antibodies, and 2) there were fewer (but not zero) cells called lymphocytes in the blood. The latter implication set up for the discovery of T cells and also illustrated that lymphocytes were not a homogenous population of small uninteresting cells and deserved further study. Anyway, cells that make antibodies were named B cells, B for bursa. The funny thing is that researchers then tried to look for a bursa in mammals but failed because mammals don't have a bursa. Mammals and most other vertebrates that aren't fish or birds make B cells from the bone marrow, thus confusing many an undergrad who naively assume B stands for bone.^[2] My point in this quick historical tangent is that avian B cell biology substantially differs in some aspects from the normal (mammalian) state of affairs.

So, how different? For one, the molecular mechanism by which avian B cells generate their repertoire of B cell receptors, i.e. antibodies. I'm going to assume the reader (you!) already knows of the mechanism by which mammals largely generate their repertoire, but Wikipedia has an entry on it. Anyway, avian B cells still undergo V(D)J recombination but the resulting repertoire is of very limited diversity due to a much smaller pool of V, D, and J segments to paste together. However, B cells then undergo a process called gene conversion in a manner analogous to what I blogged previously about in lampreys. If you didn't read that particular post, then essentially what happens is that an enzyme called AID causes DNA damage within the rearranged receptor. This then recruits a DNA repair process called gene conversion that fixes DNA damage by copying from a similar but not necessarily the exact same sequence and substituting it for the chunk of DNA containing the damage. I say not necessarily the exact same sequence because this DNA repair process normally borrows from other cognate chromosome, as diploid cells are wont to do. But what actually happens is that the repair process borrows chucks of DNA from a family of pseudo-V(D) and V genes upstream respectively of the real heavy and light chain genes. Iterative processes of this modified gene conversion introduce diversity into the initially limited V(D)J rearrangements and therefore generate antibody diversity in birds. This method of generating antibody diversity depends, in part, on the physical distance between the donor pseudogenes and the actual receptor gene. That is, the closer a donor is to the acceptor, the more likely that donor is used in gene conversion. The end result is that the distances between all the component parts of the heavy and light chain loci have to be shorter than is the case in mammals. By way of comparison, the chicken light chain locus is about 25 kb; the human lambda chain locus is about 885 kb. So, small genome, small Ig locus. As we'll see, the miniaturisation of avian genomes seems to have miniaturised everything, from intergenic spaces to introns and also the Ig loci. So provisionally, it seems likely that the evolution of a small genome was a necessary pre-adaptation for the unique aspects of avian B cell biology.

Edited Oct. 11, 2010 for clarity

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1. Gregory TR. 2002. A bird's-eye view of the C-value enigma: genome size, cell size, and metabolic rate in the class Aves. Evolution. 56(1):121-130.

2. As I'm writing this, I keep thinking of those interactive toys that teach kids about farm animals. I'll tell you, higher education would be a breeze if all I did everyday is to play with toys.

Birth control

Scanning through the Globe and Mail, as per my habit every morning, I came across an editorial by Lysiane Gagnon that critiqued a column by Diane Francis. In the editorial she expresses her opposition to Ms. Francis's thesis that a global one-child policy is a viable strategy for controlling resource usage and for "saving the world" from consequences such as environmental degradation and climate change. Indeed, the byline is "Adopting China's one-child policy won't save the Earth".

What absolute shit. It's very easy to dismiss a contrary view by linking it to spectres of communism and tyranny, as Ms. Gagnon applied artlessly to Ms. Francis's column. In my experience, such tactics are applied to cover for deficiencies in analysis. Ms. Gagnon's article was more about expressing her revulsion of China's one-child policy than it was about refuting its feasibility and viability. I'll say right off the bat that China's one-child policy is not perfect, not even close. As Ms. Gagnon's article mentions, there are abuses such as forced abortions and sterilisations by elements of a corrupt Chinese bureaucracy to enforce the policy. However, this doesn't mean that the one-child policy cannot be implemented feasibly. Indeed, the official policy is financial coercion in the guise of fines to prevent people from having a second child without approval. Moreover, China's one-child policy is not absolute and varies from population to population and from region to region. For instance, ethnic minorities and rural populations are allowed to have more than one child without approval as a form of affirmative action and to prevent male-biased child selection. Even Shanghai, a huge urban metropolis, has loosened restrictions on having children due to the excessive success of the one-child policy. There are nuances and complexities to China's one-child policy, summarised well in the Wikipedia entry on the one-child policy, that are not mentioned in Ms. Gagnon's article. What was most egregiously offensive to me was the insinuation that the one-child policy is excessively cruel. What would be excessively cruel, Ms. Gagnon, is uncontrolled birth rates that would have kept many Chinese in poverty with all attendant consequences. Case in point? Look at India.

Ms. Gagnon also underestimates the power of religion to potentially obstruct a global one-child policy. I won't go in depth in to this, but I'll point out that the Pope, putative spiritual leader of a billion Catholics, opposes prophylactic and termination approaches to birth control. I wonder what he'd say about a global one-child policy. Actually, I wonder what any leader of an Abrahamic religion would say about a one-child policy. Likely speaking, nothing flattering.

Controlling birth rates as an end to controlling and conserving resources should be a no-brainer to anybody capable of critical thought. Yes, there are problems with how China implemented it, be it a surplus young male population, unequal application of the policy, tyrannical coercive measures like abortion, "egocentric" children (actually I'd like to refute this too but this post is getting too long), reduced tax and social support base, and other problems I haven't thought of, but the feasibility of a humane and financially-coercive one-child policy is not of doubt to me.

I would challenge Ms. Gagnon to do some research and critical thinking the next time she decides to comment on a complex issue such as population control.

Research funding in Canada makes it onto Nature

I've been sort of busy with school, but this deserves a quick post. In this week's issue of Nature, there is an opinion piece by a professor at the University of Ottawa who did some calculating with various metrics and so forth and came to the conclusion that directing more money to big research universities than what is already directed is not necessarily a good idea. Since it is only a "correspondence" piece to Nature, it doesn't really show any of his work and I don't know what to make of it.

On an unrelated note, the Gairdner awards just wrapped up three days of talks and geek love. I don't know if anyone outside of UofT can see these, but the talks were streamed live and recorded for posterity. The link is here.

Pandemic H1N1 vaccine and adjuvant in Canada

I read somewhat recently about how the pandemic H1N1 vaccine in Canada will be administered to the public in November, or about a month later than other countries. This is because the vaccine in Canada will contain a proprietary oil-emulsion adjuvant by GlaxoSmithKline called AS03. The article goes on a bit about criticism of the late dissemination, but I won't talk about that. Instead, I'd like to point out that in a short while, alum will lose its claim-to-fame as the only adjuvant licensed in Canada. I don't know if this adjuvant will receive regulatory approval in the US, but the rest of the world^[1] has already been using adjuvants besides alum, such as monophosphoryl lipid A (MPL) and another oil-emulsion adjuvant called MF59.

I've been doing some researching about how oil-emulsion adjuvants work, so that'll be my next post, but I can leave this quote here:

Alum and MF59 act on monocytes, macrophages, or granulocytes to induce cytokines that generate a local immunostimulatory environment eventually leading to DC activation. In addition they also promote monocyte differentiation into DCs. MF59 can also activate muscle cells at injection site.^[2]

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1.Well, at least Europe.

2.

De Gregorio E, D'Oro U, Wack A. 2009. Immunology of TLR-independent vaccine adjuvants. Curr Opin Immunol. 21(3):339-45.

Research dollars and governments

I've been in China for the past two months learning some Mandarin. Pretty fun stuff! and I took lots of pictures. Anyway, I saw this story on the Globe and Mail website which talked about a lobby by the large and research-intensive universities for an even greater share of money handed out by CIHR, NSERC, and SSHRC. The idea is that giving a bigger share to those already research-intensive universities will eventually create elite super-productive institutions. Since I come from a big research-intensive university, this especially appeals to me. It also makes sense. The article mentions economies of scale and critical mass of researchers translating into momentum-- sensible points, but the best point is that such hypothetical money will benefit me (possibly). Gimme money!

University presidents were contacted in the article, and obviously not all of them agreed with the proposal since many of them headed small(-ish) institutions. The best criticism of the proposal given was that by David Johnston, president of the University of Waterloo. His premise is that granting money based on past performance may exclude potential innovation by other universities, for which I guess UofW would be an excellent example since they make the news a lot with all their spin-off companies. Research in Motion, the company that makes Blackberrys, was founded by an alumnus of UofW. The criticisms given by other presidents are kinda iffy though. For instance, President Jack Lightstone of Brock University complains: "This is about tiering the university system - essentially investing in them by divesting in others." Well Mr. Lightstone, your point might make sense if the universities were not de facto tiered. If you asked a person on the street on how they would rank the University of Toronto and Brock University to one another, they would likely place the University of Toronto higher. Giving more money to an extremely productive research university rather than a small university out in the hinterlands of Ontario makes sense to me. Anyway, the research universities already attract a buttload of funding anyway so complaining about tiering is disingenuous since tiering already exists, and it doesn't address the commonsense of the proposed funding change. President Roseann Runte, president of Carleton University, suggests that such a funding change would stifle competition (amongst Canadian universities? the article in unclear) and create an professor-drain towards the big universities. Assuming Ms. Runte meant competition amongst Canadian universities, I think the best rebuttal is that the big Canadian universities compete on the world-level. Giving them more money makes them compete better amongst scholastic giants. Talking about competition in Canada seems almost... provincial. I don't know about her point about professor-draining because I don't understand completely on how professors are hired and tenured, but I doubt a massive exodus of talent would happen if funding were biased to the big universities. Even if it did happen, how is a drain bad? :)

I think, however, the presidents of all universities would agree that increased government spending into research is a good idea. The brouhaha over the Harper government's slashing of the granting agencies' budgets is foremost in my mind right now. Apropos to this, the article quotes one Robert Birgeneau, Chancellor of the University of California at Berkeley, who advocates complete government coverage of research spending to create elite research institutions. Apparently, the UC system gives preferential spending to UCB and UCLA, both of which have name-brand recognition in the world of academia. However, covering all the research spending sounds really expensive, and the UC system isn't doing quite so well with the recession, what with the hiring and salary freezes and the firing and the professors migrating away.

Lamprey pie

Take your Lamprey and gut him, and take away the black string in the back, wash him very well, and dry him, and season him with Nutmeg, Pepper and Salt, then lay him into your Pie in pieces with Butter in the bottom, and some Shelots and Bay Leaves and more Butter, so close it and bake it, and fill it up with melted Butter, and keep it cold, and serve it in with some Mustard and Sugar

Also, I need to find a reason to leave North America or at least go to Alaska during lamprey spawning season. I got me a hankering for lamprey meat.

Lamprey adaptive immunity, part 2

So as I said previously, there are (thus far) two genes that undergo DNA recombination in lampreys, VLRA and VLR-B. Both VLR's have a very similar structure, much more so than immunoglobulin-domain based BCR's and TCR's. VLR cassettes essentially consist of an N-terminal leucine rich repeat (LRR) and a C-terminal LRR that probably serve as anchor points for gene conversion (a flavour of DNA recombination), and a stalk that anchors the VLR to the cell surface via a molecule called glycophosphatidylinositol (GPI). Pseudogene VLR's upstream and downstream of the VLR cassette copy themselves into the cassette via gene conversion (probably) to generate receptor diversity, and the end products of both VLR-A and VLR-B look fairly similar at least on a protein domain level.

Of course, VLRA and VLRB are not equivalent or else we'd have nothing to talk about. The paper I mentioned in my last post finally came out in a print edition of Nature.^[1] Max Cooper's group were able to generate antibodies specific to invariant stalk of either VLR-A or VLR-B, thus allowing them sort out blood cells by flow cytometry. They did an initial sort of the blood cells by "gating" for lymphocytes based on their characteristic size and light scattering; in that respect, lamprey lymphocytes are interestingly similar to mouse lymphocytes.^[2] Anyway, lamprey lymphocytes can sort into distinct populations of either VLRA⁺VLRB^- or VLRA^-VLRB⁺ (or double negative) cells. The fact that VLRA and VLRB are on different lymphocyte populations suggests functional differences between the two genes. Both lymphocyte populations could also be sorted fairly purely, which allowed for further characterisations. Using primers that flank the coding sequences of VLRA and VLRB, they were able to demonstrate by genomic PCR that only the VLRA gene and not VLRB was recombined in VLRA lymphocytes. Similarly, only the VLRB gene was recombined in VLRB lymphocytes. Moreover, when they quantified the band intensities of germline and mature PCR products of VLRA in VLRA lymphocytes, they were equal. This indicates that somatic recombination of VLRA only happens on one allele of VLRA, from either Mom or Dad.^[3] This monoallelism was previously reported with VLRB according to the authors. I think this is a really neat result because it fits in so well with the clonal selection hypothesis, which requires immune cells that generate variable receptors like TCR and BCR to only carry one receptor specificity. You can make sense of this by a simple thought experiment with a hypothetical immune cell with both a specificity to foreign antigen and to self-antigen. If this immune cell were to become activated by its cognate foreign antigen, it will also react against self. In order to avoid autoimmune disease, immune cells must only have one receptor specificity-- this monoallelic recombination is seen with the immunoglobulin heavy chain and TCRβ genes (although not the Ig light nor TCRα genes).

They also perform some quantitative PCR on a bunch of immune genes and demonstrate that the gene expression profiles of VLRA and VLRB lymphocytes differ from each other. In fact, blocks of expressed immune genes normally associated with T and B lymphocytes respectively were also associated with VLRA and VLRB lymphocytes. This result in and out of itself is interesting, but it's hard to say how it fits in with what's known about lamprey adaptive immunity. The same can be said with their experiment with PHA, which preferentially causes T cells to divide-- the gist is that VLRA lymphocytes preferentially proliferate after administration of PHA. I think the main thing to take away is that, indeed, VLRA and VLRB cells are not functionally the same. Quibbling aside, there are some especially interesting data like the expression of Notch1 on VLRA cells.^[4]

The real fun stuff is when they immune challenge lamprey larvae with killed anthrax spores. Both VLRA and VLRB populations proliferate after immune challenge, but curiously only VLRB cells bind to spores and only VLRB is secreted in much the same manner as antibodies. This is analogous to how only B cells bind native unprocessed antigen, and how only B cells secrete their receptor. The obvious speculative idea is that perhaps VLRA cells are like T cells, in that they don't bind native antigen, don't secrete their receptor, and have a similar gene expression profile and response to cell-specific mitogens like PHA. The authors bolster this line of speculation by pointing out the need to control how an anticipatory variable receptor repertoire is deployed, re: helper T cells. On a related note, I think that functional diversification of VLRA and VLRB cells also reflects functional diversification of lymphocytes in jawed vertebrates. For instance, other classes of T cells like CTL and T_H17 cells mediate different arms of the immune response to different pathogens in topologically-distinct compartments (i.e. intracellular/extracellular).

In summary, VLRA and VLRB lymphocytes are clearly functionally different. This may reflect certain common challenges to the evolution of adaptive immunity, such as the spectre of autoimmunity and forming responses to the huge variety of possible infectious routes. Lamprey immunity is still getting its legs, but this paper goes a long way to making a reality of a robust comparison between two separate but convergent adaptive immune systems. If even some of the speculative ideas I mentioned above can be confirmed, it would be a truly elegant validation of how we understand the evolution of adaptive immunity.

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1. Guo P, Hirano M, Herrin BR, Li J, Yu C, Sadlonova A, Cooper MD. 2009. Dual nature of the adaptive immune system in lampreys. Nature. 459: 796-801.

2. Mayer WE, Uinuk-Ool T, Tichy H, Gartland LA, Klein J, Cooper MD. 2002. Isolation and characterization of lymphocyte-like cells from a lamprey. PNAS. 99(22):14350-14355.

3. My initial reaction and that of my supervisor to the reported intensity values was that, wow, they're really close to 50:50. They did genomic PCR on populations of lymphocytes and not on single cells, which means their conclusion of monoallelism is probably correct but not beyond all doubt since it's conceivable that some lymphocytes could have recombined both alleles and some didn't recombine diddly. After some meditation, however, I think their conclusion is more than just probably correct since they used a pure VLRA lymphocyte population, which would preclude those lymphocytes with two germline VLRA alleles. In addition, the essentialness of only one receptor per a lymphocyte would undoubtedly force values very close to 50:50.

4. I looked at their phylogenetic tree of Notch1 and lamprey Notch1 does seem to cluster with Notch1 of jawed vertebrates. I presume that lampreys have more than just Notch1, but either they haven't found the other Notchs or they just didn't want to include lamprey Notch2 into their Notch tree. A quick search in Entrez didn't give me anything on lamprey Notch. Anyway, Notch1 is an absolutely necessary and sufficient signalling molecule in T cell development, which is interesting because lampreys don't have a thymus to express Notch1 ligand (Delta-like 4?). Then again, my supe reminds me that Notch used many times during development, and that VLRA cells expressing Notch doesn't mean anything without more info. So like I said, interesting.

Lamprey adaptive immunity, part 1

Ask any student of immunology about the occurrence of adaptive immunity in animal phyla and they will most likely tell you that adaptive immunity only occurs in jawed vertebrates. However, textbooks inevitably lag behind current knowledge of adaptive immunity as it has been known for a couple years now that there is a convergent adaptive immune system in jawless vertebrates (hagfish and lampreys).^[1] There’s a nice summary of lamprey adaptive immunity over at Mystery Rays. As a caveat about textbooks, I don’t have the nice apple green 7th edition of Janeway’s Immunobiology which promises new information on “findings on adaptive immune responses in lower organisms,” so I fully retract my textbook comment if it’s in there. Also, lower organisms?—bleh. Anyway, Max Cooper’s group published again in last week’s issue of Nature and it’s thought provoking.^[2] More on this later.

The basis of adaptive immunity in jawed vertebrates is constituted by B cells and T cells, thus named by their tissue of origin (bone and thymus respectively, but the B really was used for the bursa in birds where B cells were discovered). B cells make membrane-bound and soluble immunoglobulin-domain receptors called B cell receptors (BCR) and antibodies. On the other hand, T cells only make membrane-bound immunoglobulin-domain receptors called T cell receptors (TCR). The molecular basis for the generation of both these receptors is very similar. In essence, DNA recombination of various germline-encoded V, D, and J segments creates a tremendous variety of joined V(D)J segments, with extra variation thrown in by a specialised form of double strand break repair (resulting in chewing back and addition of random nucleotides at V(D)J joins) and mismatch repair initiated by activation induced cytosine deaminase (AID) and carried out error-prone DNA polymerases (only for B cells). The end result is that in every jawed vertebrate, an extremely large repertoire of receptors arises independently in each organism. Beyond the fact that B cells can secrete a soluble form of their BCR whereas T cells cannot, there are other notable differences. For instance, the TCR can only bind its particularly-sized peptide ligands that are loaded onto molecules called MHC (major histocompatibility complexes); in comparison, BCR are free to bind to peptide, protein, carbohydrate, and so on without anything analogous to MHC.

B cell activation upon binding its cognate ligand also requires T cell help, which requires that the B cell eat and process whatever its BCR binds and present it on MHC to the T cell. If the TCR on the T cell recognises that peptide—MHC complex, the T cell gives stimulatory signals to the B cell that allow it to activate. The reason for this fiddly process of T cell help is to make sure only the right B cells are activated. This is not trivial because there are B cells that have specificity towards one’s self and can mediate autoimmune disease (i.e. the immune system attacks the body). But you may ask, who watches the watchmen? Interestingly, T cells undergo a very stringent developmental check where self-reactive T cells are deleted. In terms of the number of T cell progenitors that don’t make it past V(D)J recombination and self-deletion, I think 98% is the right number (don’t quote me!). B cells have their own self-reactive deletion step but it is way less stringent.

In lampreys, VLR-A and VLR-B genes underlie adaptive immunity, and in the Nature paper I’m going to talk about, they find interesting parallels with adaptive immunity in jawed vertebrates. I’m going to make this a two-parter, but I might as well say what I feel is so interesting about this paper: it makes the case that there may be certain fundamental requirements that adaptive immunity had to achieve as demonstrated by two separate but convergent adaptive immune systems.

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1. Pancer Z, Amemiya CT, Ehrhardt GR, Ceitlin J, Gartland GL, Cooper MD. 2004. Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey. Nature. 430(6996):174-80.

2. Guo P, Hirano M, Herrin BR, Li J, Yu C, Sadlonova A, Cooper MD. 2009. Dual nature of the adaptive immune system in lampreys. Nature. Epublication ahead of print.

Cancer immunology at UofT

UofT is a hotbed of cancer research due to a combination of lots of hospitals, history, history, and various cancer research institutes born from that weighty history. Everyone Many medical doctors, cell biologists, developmental biologists, biochemists, and geneticists have a finger in the cancer pie at UofT, although this is strictly my impression and may not be true at all. Not. Anyway, I only bring it up because the Globe and Mail had an article about how researchers were able to use IL-7 to boost the effectiveness of a live viral vaccine for their cancer model. I'm usually bleh about cancer immunology... and this is no exception. I haven't read it because I should really be studying for exams, but Tak Mak is a co-author on it and I've been really curious as to what Tak Mak studies nowadays. Tak Mak is best known for cloning the T cell receptor beta gene in humans (Steve Hedrick and Mark Davis cloned TCRbeta in mice only a slight bit earlier, I think), a textbook, and being featured in annual October musings about Swedish gold. So I'll probably read this at some point and if it's interesting, I'll add it to my write-up pile.

Back to exams!

Hijacking of the victim immune response by insect venom?

I just gave a small presentation on how alum and other particulate adjuvants work via the "danger" signal system that is the NLRP3 inflammasome, with summaries here. I won't bother summarising anything here about it because it has already been done rather well at the link I just provided. I also feel lazy. Anyway while preparing my presentation, I did a last minute check on Pubmed for any new developments and apparently hyaluronan (among everything as it seems) triggers the NLRP3 inflammasome to produce IL1β.¹ Hyaluronan is a component of the extracellular matrix and it is released at a site of injury. By happenstance, I found out while trolling Google that insect venom contains hyaluronidase which obviously breaks down hyaluronan but also promotes the production of IgE and IgG1.^2,3 I think it's pretty neat that hyaluronidase in insect venom is an adaptation to adjuvant the victim's allergic response to insect stings.

yay I learned something today

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1. Yamasaki K, Muto J, Taylor KR, Cogen AL, Audish D, Bertin J, Grant EP, Coyle AJ, Misaghi A, Hoffman HM, Gallo RL. NLRP3/cryopyrin is necessary for IL-1beta release in response to hyaluronan, an endogenous trigger of inflammation in response to injury. J Biol Chem. 2009 Mar 3 (epublication ahead...) doi:10.1074/jbc.M806084200
2. King TP. (haha sorry he must have gotten shit as a kid) Venom Allergenicity: Hyaluronan Fragments Promote Ige And Igg1 Response In Mice. J Allergy Clin Immunol. 2009 Feb; 123(2): S1, page S99 doi:10.1016/j.jaci.2008.12.355
3. King TP, Spangfort MD. Structure and biology of stinging insect venom allergens. Int Arch Allergy Immunol. 2000 Oct;123(2):99-106. doi: 10.1159/000024440

What organisms can vegans work with?

I've been thinking about this, and it would seem that the only organisms that vegans can work with in biology in terms of not using any animal products would be photosynthetic or saphrotrophic organisms, maybe. I guess vegans could work in paleontology, but I think dead organisms would be an obvious exception.

Let me back up. Obviously vegans should not work with animals because poking, prodding, and killing animals wouldn't fit with their aim of not harming animals. Even observers of animal behaviour would inevitably have to harm animals in some fashion, I think. They cannot work with cell culture because cell culture requires animal products like fetal bovine serum (fetal calf serum, what's the difference anyway?) and bovine serum albumin. They cannot work with yeast or bacteria because a lot of growth media requires protein sources like hydrolysed milk casein. Ditto with most other branches of life, because ultimately I'd think one would have to use animal products somewhere in there. Even plants might be tricky especially since molecular biology has its fingers in practically every field of experimental biology including botany-- for instance, cloning plant DNA would inevitably require bacteria. Unless a vegan were content to spend their scientific career describing plants or other organisms in the most superficial way without molecular biology, then I think there really is no career in experimental biology for vegans.

I would love it if a vegan could confirm this, or otherwise correct any misconception of mine about the vegan lifestyle. Anyway, that's my small thought of the day.

Literature grinding sucks

So I have to write a fake research proposal and so far I've learned that reading lots of articles in a short time span sucks. Also, I haven't written a thing and it's due in a day-- yay! The plus side to all this reading is that I've got several topics I've been incubating in my head but so far I haven't committed them to blog. One day. But seriously, I'm going to list a few topics so that it's out there and I'll feel committed to writing about them:

• Sea urchin immunity, what I know and why we should all be interested.
  
• NK cell memory and how I'm going to draw an analogy to sea urchins.
  
• Wax disgusting over how cute cells look with two-photon microscopy. So cute!
  
• My first transgenic GFP sea urchin larva, which still has to be born...
  
• Miscellany. heh.
  

Also, I got accepted into the department of immunology at UofT, which while unsurprising is still excellent news. Huzzah!

New year. blah

So I finished a crushing semester of molecular immunology, developmental immunology, practical immunology, with electives of functional genomics and bioinformatics. I'm still afraid to check my marks, which is childish, but I think rounding out a undergraduate education has that infantilising effect. Or, perhaps, I'm getting old.

Anyway, I resolve to actually write about neat stuff I've encountered or learned. I think I didn't use this blog too much before because, well, I knew shit. I probably still know shit, but nevertheless I feel like I should share some perhaps-not-shit. Whee!

Sea Urchin Ethics

So I'm playing with purple sea urchins this summer, which I'm pretty excited about although I probably won't go into sea urchin immunity right now. But sea urchins! Like many models of development like Drosophila or C. elegans, there are minimal ethics with regard to what one can do to them, unlike traditional immunology animal models like mice. At any rate, "ethics" are wooly in my opinion because the ultimate reason it seems for why chordates get special consideration is morphological similarity. Doubtlessly many people have had metaphysical discussions about "ethics" and their anthropocentric derivation, so I won't belabour the point. However, one of the ethical considerations when working with sea urchins is that one must promise not to eat them.

Yeah, I laughed too when I heard that, mainly because I was secretly thinking about it. In all likelihood, they'd be just as delicious as those found in culinary establishments because we get our sea urchins fresh from the Pacific (no one raises them because they're dead easy to harvest, with the added plus of removing kelp forest predation). However, the ones we get are pretty small (biggest are about two inches diameter not including the spikes), and when you take in account that only the gonads are edible, they're not much of a meal. Furthermore, the lab I'm working in works a lot with sea urchin larvae, the formation of which apparently depletes sea urchin gonads and results in their shrinking (sea urchins that spawn get to see the inside of a -20 degrees Celsius freezer unfortunately because no one knows how to make them spawn again and it's too easy to harvest fresh ones). And the best reason why I won't be eating sea urchins this summer is because they're actually pretty cute with their tube feet (one thing that I didn't know sea urchins had until recently).

Anyway, I have this neat blog post to thank for getting me interested in sea urchin immunity: http://www.iayork.com/MysteryRays/2007/09/01/42/