It’s Alive!

Over an end of semester dinner with classmates last night I encountered what I had always thought impossible: a frank and honest discussion about religion that didn’t end in me wanting to slap someone in frustration. In fact, I would go so far as to say that I found it profoundly insightful.

I’m an avid Pharyngula reader and a big Dawkins fan, but usually steer clear of the Science vs Religion debates that are awash throughout the blogosphere. Not because I don’t have an opinion, but because it’s a huge topic area and for the most part I just can’t be bothered. Also, it always seems to be the same stuff going around and around ad nauseum.

And it’s for these same reasons that religion doesn’t usually form part of my dinner time conversation repertoire. It’s more the domain of drunken ranting, particularly with one of said classmates who I have enjoyed numerous alcohol induced religious arguments with.

My classmates are all very smart, knowledgeable and critical young scientists, but I did not really understand how this could be reconciled with their religious beliefs (they’re all Catholic) until our conversation last night. It turns out that their beliefs are much more rational than I had preconceived.

At the root of it, their concept of God is pretty much the same as my concept of the scientifically unknown. They believe in evolution, the big bang, and explaining natural phenomena through science. They do not believe God dictates their actions or controls their destinies, and they do not pray for divine intervention in the minutia of their daily lives.

The only real difference between myself and them is that I don’t mind the idea that the universe is the be all and end all (in fact, I live in a constant state of awe at this concept), while they find a wee bit of comfort in thinking that beyond all this there is some divine force that they just so happen to call God.

I can sympathise with this concept of religion, and don’t find it that irrational. I don’t really see a huge disparity between believing that beyond the ends of the universe there exists either nothing or some omnipotent force. The concept of god does not explain the universe, it just exists as a sort of mental safety net for when we get beyond the bounds of our imagination. I don’t believe it, but I can understand why so many people do.

Importantly, this discussion also helped me to realise that it’s probably not the best idea to lay my preconceptions about religion on anybody who calls themselves a christian. While I do have a fairly sound understanding of christianity (I went to a Catholic school AND i’ve read The Da Vinci Code) I have been reading Dawkins and PZ Myers for way too long without stopping to think that not all religious types are irrational and close minded.

That said, the rational academic christian is definitely in a different league to the crazed religious zealots that mascarade their doctrines as pseudo scientific theory.

(new edit: A similar conclusion is drawn after a hefty yet eloquent discussion on the philosophy of science by Dr Freeride)

My MSc thesis is now on the shelf in the University of Otago medical library, almost six months after I first submitted it for examining. Unfortunately, receiving it back from the examiners last year coincided with my shift over to Edinburgh, so making the suggested corrections and formally submitting it took a bit of a back seat to drinking, making new friends, and starting a PhD.

But now it is sitting in the dark, musty, windowless thesis room deep in the bowels of the library, just waiting to impart its awesome glory on whoever stumbles accross it.

Continuing my new trend of spending waay too much time trying to finish my lab work for the semester instead of being permanently connected to my laptop, I only have time today for a brief video post on the theme of science and dancing.

As anybody reading this will likely know, the Youtube video Evolution Of Dance is oft quoted as the most popular YouTube video of all time, with over 78 million page views.

But now, I think we may have a new contender.This video takes everything good about the aforementioned video, and makes it better. How does it do this? Simply by replacing the guy with arguably the best robot ever: Optimus Prime.

Why this has only received a meagre 200,000 views to date is quite beyond me.

Although fortunately a friend from back home sent me the latest album from one of my favourite NZ bands, the Phoenix Foundation, entitled Happy Ending, which has helped keep me from jumping out the lab window.

I’m drawing to the close of my research project for the semester so am obviously spending this week doing all the experiments I should have been doing for the past two months in a mad attempt to get enough data to write a coherent report about. Have spent 12 hours or so every day this week doing nothing but HPLC to measure the effects of up or down regulation of a particular serotonin receptor (5HT2CR…if you’re asking) in a couple of lines of transgenic mice we have in the lab. While interesting in theory, the actual lab work involved in preparing and running each sample is very mundane, thus this album was a welcome addition to the lab-work playlist on my iPod.

And since these experiments have cut the umbilical cord I share with my laptop on most days, this post is all I have had time to come up with all week (which is a token effort, at best). Anyways, here’s the retro-tastic beast of a video clip for the first single off said album, Bright Grey.

If baldness is really a genetic trait, then I am well and truly screwed. I come from a long line of cue balls; every male in my family over the age of 30 is bald or balding. Especially worrying is the fact that both my Dad and my maternal Grandfather started thinning in their mid twenties, a fact my Dad takes particular glee in pointing out to me at every available opportunity.

Thus, I greeted a couple of recent articles in Nature Genetics with an air of optimistic hope. Of particular interest to me is the paper by Pasternack et al (citation below), which details a complete a start-to-finish study on the genetics of a rare hair loss disorder, beginning with a genome wide linkage analysis and ending in functional characterisation of the candidate gene: P2Y5. A simultaneous article in the same journal also looked at the involvement of this gene in hair growth, but from a different functional perspective, as covered over at Gene Expression.

Due to the commonality of baldness and the complex pathophysiology of hair growth disorders, finding a genetic cause with therapeutic potential is extremely difficult. This is why studying rare heritable hair loss disorders, such as the specific alopecia condition analysed in this study, offers a unique opportunity to pinpoint some of the key components involved in maintaining normal hair growth.

A powerful approach to advance our understanding of the pathophysiology of human hair loss is to identify genes underlying mendelian isolated alopecias. Investigation of this type of hair loss offers the unique opportunity to identify factors that are not only necessary for, but also specific to, hair growth.

Using an affected Saudi Arabian family, the group mapped the disease locus to a 28Mb region on chromosome 13. Candidate gene sequencing revealed a truncating mutation in the sequence for P2Y5: a gene that codes for a G protein-coupled transmembrane receptor. Normally located on the cell membrane, the group showed accumulation of the truncated protein in the endoplasmic reticulum, suggesting loss of function.

Aside from the solid genetic analysis carried out, the real strength of this paper lies in the further functional analysis of the protein, which did not have a clearly understood function. Through a reporter gene assay and A radiolabelled binding experiment, the group identified lysophosphatidic acid (LPA) as the ligand for the receptor. In addition, they demonstrated in vitro that the truncated version of this protein is unable to elicit the cellular response normally observed after binding of LPA to P2Y5, likely due to the loss of a number of intra-cellular loops that are known to be involved in G protein activation.

LPA is known to bind a number of receptors alongside P2Y5, with a downsteam effect of enhanced cell proliferation and migration. Broadly, these receptors can be classified into two subgroups: LPA1, LPA2 and LPA3 in one group, and LPA4 and LPA5 in the second group. The authors propose the placement of P2Y5 in with this latter subgroup due to its amino acid sequence homology and the similar downstream signalling pathways.

Interestingly, of the latter group of receptors, LPA4 and LPA5 are not expressed in the hair follicle. Thus, a loss of the one member of the group that is, P2Y5, leads to a complete loss of LPA signal transduction through the specific pathway mediated by the group. Further characterisation of this pathway is now required in order to understand how its impairment results in the alopecia phenotype observed in affected individuals however.

Ultimately, the most important question to arise from this study to me is: could it eventually culminate in an effective treatment (or even a cure!) for baldness? While it is conceivable that this paper offers the possibility of identifying potential inducers of the LPA-P2Y5 mediated pathway in a hope of enhancing hair growth in balding individuals, more realistically it offers potential for further elucidation of the complex pathways involved in hair follicle development and function.

Thus, I don’t think I’ll be seeing any wonder-drugs in the crucial next few good-hair years I have left in me that will cease the inevitable chrome-domia before it advances into chronic cue ball-ness.

Pasternack, S.M., von Kugelgen, I., Aboud, K.A., Lee, Y., Ruschendorf, F., Voss, K., Hillmer, A.M., Molderings, G.J., Franz, T., Ramirez, A., Nurnberg, P., Nothen, M.M., Betz, R.C. (2008). G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth. Nature Genetics, 40(3), 329-334. DOI: 10.1038/ng.84