Executive one line summary: I research into the genetic causes of rare diseases using genomic technologies and like to complain a lot 😀

Monkol Lek completed PhD degree in human genetics in the Faculty of Medicine at the University of Sydney and Institute for Neuroscience and Muscle Research in 2012. He also has three bachelor degrees from the University of New South Wales in Bioinformatics, Science (Physiology and Statistics) and Computer Engineering. He currently works as a senior research fellow in the MacArthur lab at Massachusetts General Hospital and is affiliated with the Broad Institute of MIT and Harvard, Harvard Medical School and the University of Sydney. The stuff below was originally written 2011-2012 and I’m too lazy to edit 🙂

After completing a BE (Computer Engineering), I gained 3.5 years industry experience at IBM working as a certified IT Security Professional (CISSP, CCNA, CCDP, MCP) and Applications Developer. The web application suite I built using open source software (Apache, PHP, MySQL) provided the initial framework for all contractual security tasks to be tracked. Due to its success in Australia, this was then used in IBM Asia Pacific and then went global in 2011 Q1 after many modifications and improvements.

Unfortunately, I was not around to see my efforts flourish as I jumped ship to join academia because of two reasons. First, I was diagnosed with a late onset muscle disease. Second, I realized my skills was doing nothing but making people rich. I had much greater plans for my skills and time. I went back to University to do a BE (Bioinformatics)/BSc (Physiology) double degree. I actually did more molecular biology and genetics courses than those majoring in it as I had exhausted all the computing electives the first time round 😛 I completed in 2007 receiving the UNSW medal for finishing first in my Bioinformatics degree. I felt bad because I spent the last 2 years of my degree playing online poker 12 hours a day instead of attending lectures and tutorials.

My PhD research project is to explore the functional difference between two similar muscle proteins, α-actinin-2 and α-actinin-3. The reason why α-actinin-3 (coded by ACTN3) is a gene of extreme interest is that there is a common nonsense polymorphism (R557X) in human populations. It is estimated that approximately ONE billion world-wide are completely α-actinin-3 deficient with no obvious disease. The 577R allele has been shown to be advantageous in activities that require muscle power and strength with all elite Australian sprinters having two copies of this allele. Alternatively, the 577X allele could be considered detrimental to sprint activities. In addition, our lab has shown that the 577X allele has been positively selected in Euroasian populations and was published in Nature Genetics along with our Actn3 KO mouse. Unfortunately I joined the lab, shortly after this massive publication 😥 My research is best explained in my Bioessays review (1) paper (features on the issue cover) and a blog in Pharyngula which is based on the same review paper. I have studied the function of α-actinin-3 both at a evolutionary level (2) and a protein-protein interaction level (3,4). My 4 major publications are below. I currently have 9 publications in total during my PhD research.

1. Lek M, Quinlan KG, North KN. The evolution of skeletal muscle performance: gene duplication and divergence of human sarcomeric alpha-actinins. Bioessays. 2010 Jan;32(1):17-25. Review. PubMed PMID: 19967710.

2. Lek M, MacArthur DG, Yang N, North KN. Phylogenetic analysis of gene structure and alternative splicing in alpha-actinins. Mol Biol Evol. 2010 Apr;27(4):773-80.  PubMed PMID: 19897525.

3. Lek M, North KN. Are biological sensors modulated by their structural scaffolds? The role of the structural muscle proteins alpha-actinin-2 and alpha-actinin-3 as modulators of biological sensors. FEBS Lett. 2010 Jul 16;584(14):2974-80.  Review. PubMed PMID: 20515688.

4. Seto JT, Lek M, Quinlan KG, Houweling PJ, Zheng XF, Garton F, MacArthur DG, Raftery JM, Garvey SM, Hauser MA, Yang N, Head SI, North KN. Deficiency of α-actinin-3 is associated with increased susceptibility to contraction-induced damage and skeletal muscle remodeling. Hum Mol Genet. 2011 Aug 1;20(15):2914-27. PubMed PMID: 21536590.

Outside my main research project, I am interested in the analysis of Next Generation Sequencing data. In particular the 1000 genomes variants in muscle disease causing genes to assess the difficulty in identify novel disease causing mutations and also the carrier status in the general population. In January 2011 with the support of key lab heads, I wrote the successful NHMRC equipment grant which funded our Ion Torrent PGM purchase. I have been quite busy setting up and managing the Ion Torrent. I decided to work on the Ion Torrent Accuracy Challenge, while waiting for our Ion Torrent PGM. It took 2 months just to get through our University purchasing system.. way to go Usyd 😛 I have been working on the accuracy challenge since February even before it was officially opened in mid-April. The Ion Community provided raw data so that I could work with. Although, the ion-Analysis code had scarce comments I was able to figure most things out as I have had a lot of experience reverse engineering, which I will not share :P. I have decided to share all my knowledge of what I have learned over the last few months as a way of getting publicity for the important work performed at the Children’s Hospital.

In addition, to researching what makes muscle strong our lab’s main focus is muscle disease research and diagnosis. There are approximately 60 genes which are associated with common muscle diseases and many diseases presenting with very similar clinical phenotypes and disease progression. This has made finding disease mutations a slow and laborious task. Our lab invested in the Ion Torrent PGM with the hope that we can find disease mutation in our large undiagnosed cohort in a more efficient and cost effective manner. Finding the disease causing mutation will bring hope back in the family and carers of children with these crippling diseases. I have been fortunate and have had a relatively normal childhood. Most of these children have never run and played in their lives 😥 Although it is not a cure, it will allow health care professionals plan preventative measure to ensure high quality of life of these children for as long as possible.

This is what drives me to blog each day. By blogging on a hot topic such as the promise and potential of the Ion Torrent for disease diagnosis also brings the attention and publicity for our cause – The fight against muscular dystrophy!