Featured Grad Paper: Ryan Gillespie

Ryan Gillespie

GSK-3 function in bone regulates skeletal development, whole body metabolism and male lifespan

 

Gillespie JR, Bush JR, Bell GI, Aubrey LA, Dupuis, H, Ferron M, Kream B, DiMattia G, Patel S, Woodgett JR, Karsenty G, Hess DA, Beier F

Endocrinology. First published ahead of print July 31, 2013 as doi:10.1210/en.2013-1155

 

This article was also a Research Highlight in Nature Reviews:
Bone: GSK-3β in bone might also regulate whole-body metabolism.
Nat Rev Endocrinol. 2013 Aug 13. doi: 10.1038/nrendo.2013.164. [Epub ahead of print]
http://www.nature.com/nrendo/journal/vaop/ncurrent/full/nrendo.2013.164.html

Summary of paper in Ryan’s words:

Ryan Gillespie“Please excuse me if I get a little excited talking about this paper as it was a long study spanning the length of my PhD and the submitting process was long and drawn out - to say the least. There are two important findings that I will highlight.  We produced osteoblast-(bone forming cells) specific deletion of glycogen synthase kinase 3 beta (GSK-3b).  GSK-3b is a “brake” on many anabolic pathways, such as Wnt and Insulin pathways.  We expected that knocking out (KO) the GSK-3b gene would increase growth, but we found that the mutant mice were smaller by weight from birth, although the size of their skeleton was normal.  This meant that weight was being lost from another tissue.  Through the Advanced Facility for Avian Research (AFAR), we used quantitative magnetic resonance (QMR) to determine that the reduced weight was almost entirely due to fat loss.  This indicated that bone was affecting whole body metabolism, which is not an entirely new concept but a very hot and controversial topic in the bone field.   Ryan GillespieWe examined blood glucose and insulin levels and found that both were reduced in our KO mice.   Usually, when insulin levels are low, glucose is high.  Interestingly, we found that the mutant mice were more insulin-sensitive, thus explaining our findings.  In other words, less insulin would be needed to reduce blood glucose levels in KO mice.   Finally, the most surprising and interesting finding is that, while attempting to age the KO mice for another study, we found that almost 100% of the male KO mice died prematurely while female mice seemed unaffected.  So why were the male mice dying?  We observed several changes in the male mice that could suggest the reason of their demise, such as increased blood glucose and large bladder.  The same male mice that had low blood glucose early in life switched to high blood glucose, which is indicative of developing type II diabetes (ie.  becoming insulin-resistant).  The large bladder was harder to explain, but we found evidence of damage throughout the urogenital tract, including in the kidneys, which showed signs of hydronephrosis.  All these findings have been shown to be complications in both mice and humans with type II diabetes.  Who would have thought that deleting a gene in bone cells would cause whole body metabolic effects that results in male-specific development of diabetes and ultimate death?  It was an interesting ride and I’m glad people can read about it now.”

Ryan’s Bio:

Ryan GillespieI never do things the straightforward way and how I ended up here is no exception.  I finished undergrad at Waterloo in Biochemistry where I did my co-op placements in a sewage treatment plant (smelly!!), Petro-Canada (blending oils), and ministry of the environment (toxicity testing).  When I was nearing the end I freaked out, I had no idea what I wanted to do.  I ended up applying to teachers college and headed to France for 4 months to work at a summer camp.  I worked all over France from the Pyrenees, to Dijon, to Brittany with time off to travel around.  I returned to complete teachers college at U of T OISE to teach high school Chemistry and Environmental Science, then returned to France for another 5 months. This was a big turning point in my life as I returned to Canada after the hiring had been done for the school year, which began a very difficult period of my life of being unemployed, living at home, and having my self-esteem hit all time lows.  It was painful, but it forced me to do a lot of soul searching and I started to apply to science jobs as well as teaching jobs.  I found that I was becoming more and more interested in the science jobs - then the life changing miracle moment occurred:  I came across a posting on a random website stating: work hands on in science, teach science, get paid and get a degree and all that was required was a “love of science”.   As I remember it, the posting shone 10x brighter, my hair blew back (I don’t have any J), and I knew this was the next segment of my journey.  This posting was, of course, a grad student position in Physiology and Pharmacology. So I came to Western to do my Masters.  The day I left for London, I received a phone call from the school board, which I think is very poetic.  I loved the science (for the most part), and I loved TAing, and I knew I wanted to continue on to do a PhD - but in different lab with a different project.  This decision would cost me a couple years starting over from scratch, but it was one of my best decisions, bringing me to Frank Beier’s Lab and the aforementioned GSK-3b project. I also, prior to joining the lab, took another trip to France, which also had life changing consequences.  I was taking a train from Paris to a small village in the Brittany region.  The train stopped past the platform for some reason and we had to get out onto a pile of rocks.  When I was down and started to walk away I turned around and noticed this beautiful woman struggling with her many, many bags.  I offered to help her and we have now been married almost 6 yrs.  I’ve since graduated with a PhD!!! I am now working part time in the Beier lab and trying to pick up as much teaching as possible and I’m excited to see what life brings next. Thanks for reading this!

 Ryan Gillespie

Innovation and Excellence in Research and Teaching