The Gene SMART Study aims to identify genes and molecular mechanisms underlying the variable response to similar exercise training.

The study is ongoing; male and female participants are welcome.

About the Gene SMART study

Victoria University has received funding from the Australian Research Council (ARC) and the National, Health and Medical Research (NHMRC) to conduct the Gene SMART (Skeletal Muscle Adaptive Response to Training) Study.

The Gene SMART Study, led by Associate Professor Nir Eynon and conducted by his group ‘Genetics and Epigenetics of Exercise’,  aims to identify genes and molecular mechanisms (e.g., epigenetics) contributing to the variable responses to similar exercise training and the ageing processes.

For example, one of the genes that influences the response to exercise is the human speed gene (α-actinin-3 or ACTN3), which encodes for an actin-binding protein in skeletal muscle.

About 20% of the world population has a common variation of this gene and consequently completely lacks this protein, which ultimately influences muscle function and exercise performance.

Media appearances

Researchers have appeared in the following programs talking about the research study:

Benefits of participating in this study

The study is ongoing. Results from past and current participants are being analysed. Male and female participants still welcome.

We are looking for 18- to 45-year-old men and women to participate in a 4-week high-intensity exercise program to assess their Skeletal Muscle Adaptive Response to Training (SMART).

As a research participant you will:

  • be offered a cash reimbursement of $100 for your time
  • train in state-of-the-art facilities at our Footscray Park Campus supervised by qualified sport scientists with years of experience
  • be provided with feedback on your performance in various fitness tests (VO2max, lactate threshold, and peak power) and gain a greater understanding of your own fitness
  • potentially gain significant fitness improvements.

From your participation in this project you will gain experience and knowledge on how physiology and molecular studies are undertaken, which might be beneficial for your own understanding of the human body.

What participants are required to do

Participants are asked to give between 20 and 30 hours of their time over approximately 9 weeks.

This involves the following phases:

  • familiarisation testing
  • baseline testing
  • control phase
  • control testing
  • training phase
  • post testing.

You'll need complete the following:

  • fill out an informed-consent form and exclusion criteria questionnaires (15 minutes)
  • a 20km time trial on a stationary cycling ergometer (approx. one hour)
  • a graded-exercise test and maximal-oxygen-uptake test on a stationary lode bike (approx. one hour).

This phase takes place over one week.

You'll complete these exercises and tests:

  • a 20km time trial (approx. one hour)
  • two graded-exercise tests and maximal-oxygen-uptake tests (approx. one hour each)
  • control biopsy and blood sampling (approx. 45 minutes).

Over 4 weeks you'll carry on with your usual activity level, wearing an activity monitor for 2 weeks.

After the control phase, the initial testing will be performed again to assess any changes to your fitness from your regular activity levels.

You'll complete these exercises and tests:

  • a 20km time trial (approx. one hour)
  • two graded-exercise tests and maximal-oxygen-uptake tests (approx. one hour each).

Once control testing is complete, you'll begin the 4 weeks of High Intensity Interval Training (HIIT).

You'll complete these exercise sessions and tests:

  • three exercise trial biopsies during the first HIIT session (approx. 4 hours)
  • eleven further HIIT sessions (25 to 45 minutes).

Once 4 weeks of training is finished, you'll have the final testing and biopsy.

You'll complete these exercise sessions and tests:

  • resting biopsy and blood sampling (approx. 45 mins)
  • a 20km time trial (approx. one hour)
  • two graded-exercise tests and maximal-oxygen-uptake tests (approx. one hour each).

Explanation of the tests & training sessions in this study

There are a variety of tests and training sessions used in this study.

Graded-exercise tests (GXT) & maximal-oxygen-uptake (VO2max) tests involve cycling on a stationary lode bike.

You'll cycle for four-minute stages of progressively increasing intensity, with 30-second rest periods.

The total time required to complete this test is approximately one hour.

This test will be used to determine the intensity at which you will be training. Seven minutes after the end of the GXT, you'll perform a VO2max.

For this test you will cycle continuously at an intensity slightly greater than that at which you stopped during the graded-exercise test. The test ends when you can no longer keep up the required pace, and will take no longer than five minutes to complete.

Throughout this test you will wear a mask which we will use to analyse the air you breathe out. This will allow us to determine your maximal oxygen uptake, essentially a measure of your aerobic fitness.

The 20km cycle time trail starts with a 5-minute warm up.

Following 2 minutes of rest, you will be required to complete the 20km cycle time trial in the quickest possible time.

During the time trial, power output measures and time will be concealed from you. However, you will be permitted to monitor your progress through completed distance and will be provided with verbal encouragement during the test.

Training sessions are completed on an electronically-braked cycle ergometer (Velotron, Racer Mate Inc, Seattle, USA) preceded by a 5-minute warm up.

Each session will consist of 8-14 two-minute intervals performed at different intensities interspersed with 1-minute recovery periods (work-to-rest ratio of 2:1).

To maintain progression, we will change the number of intervals per session and the intensity (resistance).

The purpose of a muscle biopsy is to examine the muscle in detail using a number of techniques we have available.

A qualified and experienced doctor will perform each muscle biopsy. The technique involves first cleaning the skin above the part of your thigh where the biopsy is taken.

A local anaesthetic is injected into the skin where the biopsy will be taken. This will cause a slight stinging sensation. Once the numbness has set in a small incision is made with a scalpel, and the biopsy needle is inserted into your thigh muscle, and a small amount of muscle is taken out (maximum of 0.2 gram).

The biopsy takes about ten seconds and you'll feel some pressure in your leg and possibly some pain during the procedure. Pressure is then applied to the muscle to ensure there is minimal swelling.

Contact the project team

Associate Professor Nir Eynon
Email: nir.eynon@vu.edu.au
Phone: +61 3 9919 5615

Dr Danielle Hiam
Email: danielle.hiam@vu.edu.au
Phone: +61 3 9919 4000

Dr Sarah Voisin
Email: sarah.voisin@vu.edu.au
Phone: +61 3 9919 9471

Dr Xu Yan
Email: xu.yan@vu.edu.au
Phone: +61 3 9919 4024

Macsue Jacques, PhD Candidate
Email: macsue.jacques@live.vu.edu.au

Shanie Landen, PhD Candidate
Email: shanie.landen@live.vu.edu.au

Javier Alvarez Romero, PhD Candidate
Email: javier.alvarezromero@live.vu.edu.au

Voisin S, Jacques M, Lucia A, Bishop DJ, Eynon N.
Statistical Considerations for Exercise Protocols Aimed at Measuring Trainability. Exerc Sport Sci Rev. 2018 Oct 16. doi: 10.1249/JES.
PMID: 30334853

Del Coso J, Hiam D, Houweling P, Pérez LM, Eynon N, Lucía A
More than a 'speed gene': ACTN3 R577X genotype, trainability, muscle damage, and the risk for injuries. Eur J Appl Physiol. 2018 Oct 16. doi: 10.1007/s00421-018-4010-0. Review.
PMID: 30327870

Houweling PJ, Papadimitriou ID, Seto JT, Pérez LM, Coso JD, North KN, Lucia A, Eynon N.
Is evolutionary loss our gain? The role of ACTN3 p.Arg577Ter (R577X) genotype in athletic performance, ageing, and disease. Hum Mutat. 2018 Dec, 39(12):1774-1787. doi: 10.1002/humu.23663. Epub 2018 Nov 8.
PMID: 30281865

Yan X, Dvir N, Jacques M, Cavalcante L, Papadimitriou ID, Munson F, Kuang J, Garnham A, Landen S, Li J, O'Keefe L, Tirosh O, Bishop DJ, Voisin S, Eynon N.
ACE I/D gene variant predicts ACE enzyme content in blood but not the ACE, UCP2, and UCP3 protein content in human skeletal muscle in the Gene SMART study.
J Appl Physiol  2018 Sep 1, 125(3):923-930. doi: 10.1152/japplphysiol.00344.2018. Epub 2018 Jun 21.
PMID: 29927735

Willems SM, Wright DJ, Day FR, Trajanoska K, Joshi PK, Morris JA, Matteini AM, Garton FC, Grarup N, Oskolkov N, Thalamuthu A, Mangino M, Liu J, Demirkan A, Lek M, Xu L, Wang G, Oldmeadow C, Gaulton KJ, Lotta LA, Miyamoto-Mikami E, Rivas MA, White T, Loh PR, Aadahl M, Amin N, Attia JR, Austin K, Benyamin B, Brage S, Cheng YC, Cięszczyk P, Derave W, Eriksson KF, Eynon N, Linneberg A, Lucia A, Massidda M, Mitchell BD, Miyachi M, Murakami H, Padmanabhan S, Pandey A, Papadimitriou I, Rajpal DK, Sale C, Schnurr TM, Sessa F, Shrine N, Tobin MD, Varley I, Wain LV, Wray NR, Lindgren CM, MacArthur DG, Waterworth DM, McCarthy MI, Pedersen O, Khaw KT, Kiel DP; GEFOS Any-Type of Fracture Consortium, Pitsiladis Y, Fuku N, Franks PW, North KN, van Duijn CM, Mather KA, Hansen T, Hansson O, Spector T, Murabito JM, Richards JB, Rivadeneira F, Langenberg C, Perry JRB, Wareham NJ, Scott RA.
Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness. Nat Commun. 2017 Jul 12;8:16015. doi: 10.1038/ncomms16015.
PMID: 29313844

Papadimitriou ID, Lockey SJ, Voisin S, Herbert AJ, Garton F, Houweling PJ, Cieszczyk P, Maciejewska-Skrendo A, Sawczuk M, Massidda M, Calò CM, Astratenkova IV, Kouvatsi A, Druzhevskaya AM, Jacques M, Ahmetov II, Stebbings GK, Heffernan S, Day SH, Erskine R, Pedlar C, Kipps C, North KN, Williams AG, Eynon N.
No association between ACTN3 R577X and ACE I/D polymorphisms and endurance running times in 698 Caucasian athletes. BMC Genomics. 2018 Jan 3;19(1):13. doi: 10.1186/s12864-017-4412-0.
PMID: 29298672

Williams CJ, Williams MG, Eynon N, Ashton KJ, Little JP, Wisloff U, Coombes JS.
Genes to predict VO2max trainability: a systematic review. BMC Genomics. 2017 Nov 14;18(Suppl 8):831. doi: 10.1186/s12864-017-4192-6. Review.
PMID: 29143670

Vlahovich N, Hughes DC, Griffiths LR, Wang G, Pitsiladis YP, Pigozzi F, Bachl N, Eynon N.
Genetic testing for exercise prescription and injury prevention: AIS-Athlome consortium-FIMS joint statement. BMC Genomics. 2017 Nov 14;18(Suppl 8):818. doi: 10.1186/s12864-017-4185-5.
PMID: 29143596

Yan X, Eynon N, Papadimitriou ID, Kuang J, Munson F, Tirosh O, O'Keefe L, Griffiths LR, Ashton KJ, Byrne N, Pitsiladis YP, Bishop DJ.
The gene SMART study: method, study design, and preliminary findings. BMC Genomics. 2017 Nov 14;18(Suppl 8):821. doi: 10.1186/s12864-017-4186-4. Review.
PMID: 29143594

Eynon N, Voisin S, Lucia A, Wang G, Pitsiladis Y.
BMC Genomics. 2017 Nov 14;18(Suppl 8):825. doi: 10.1186/s12864-017-4184-6.
PMID: 29143593

Massidda M, Voisin S, Culigioni C, Piras F, Cugia P, Yan X, Eynon N, Calò CM.
ACTN3 R577X Polymorphism Is Associated With the Incidence and Severity of Injuries in Professional Football Players.
Clin J Sport Med. 2017 Aug 24. doi: 10.1097/JSM.0000000000000487.
PMID: 28817413

Levinger I, Yan X, Bishop D, Houweling PJ, Papadimitriou I, Munson F, Byrnes E, Vicari D, Brennan-Speranza TC, Eynon N.
The influence of α-actinin-3 deficiency on bone remodelling markers in young men. Bone. 2017 May;98:26-30. doi: 10.1016/j.bone.2017.02.010. Epub 2017 Feb 22.
PMID: 28254467

Yang R, Shen X, Wang Y, Voisin S, Cai G, Fu Y, Xu W, Eynon N, Bishop DJ, Yan X.
ACTN3 R577X Gene Variant Is Associated With Muscle-Related Phenotypes in Elite Chinese Sprint/Power Athletes.
J Strength Cond Res. 2017 Apr;31(4):1107-1115. doi: 10.1519/JSC.0000000000001558.
PMID: 27442335

Wang G, Tanaka M, Eynon N, North KN, Williams AG, Collins M, Moran CN, Britton SL, Fuku N, Ashley EA, Klissouras V, Lucia A, Ahmetov II, de Geus E, Alsayrafi M, Pitsiladis YP.
The Future of Genomic Research in Athletic Performance and Adaptation to Training.
Med Sport Sci. 2016;61:55-67. doi: 10.1159/000445241. Epub 2016 Jun 10. Review.
PMID: 27287077

Yan X, Papadimitriou I, Lidor R, Eynon N.
Nature versus Nurture in Determining Athletic Ability. Med Sport Sci. 2016;61:15-28. doi: 10.1159/000445238. Epub 2016 Jun 10. Review.
PMID: 27287074

Voisin S, Guilherme JP, Yan X, Pushkarev VP, Cieszczyk P, Massidda M, Calò CM, Dyatlov DA, Kolupaev VA, Pushkareva YE, Maciejewska A, Sawczuk M, Lancha AH Jr, Artioli GG, Eynon N.
ACVR1B rs2854464 Is Associated with Sprint/Power Athletic Status in a Large Cohort of Europeans but Not Brazilians. PLoS One. 2016 Jun 2;11(6):e0156316. doi: 10.1371/journal.pone.0156316. eCollection 2016.
PMID: 27253421

Papadimitriou ID, Lucia A, Pitsiladis YP, Pushkarev VP, Dyatlov DA, Orekhov EF, Artioli GG, Guilherme JP, Lancha AH Jr, Ginevičienė V, Cieszczyk P, Maciejewska-Karlowska A, Sawczuk M, Muniesa CA, Kouvatsi A, Massidda M, Calò CM, Garton F, Houweling PJ, Wang G, Austin K, Druzhevskaya AM, Astratenkova IV, Ahmetov II, Bishop DJ, North KN, Eynon N.
ACTN3 R577X and ACE I/D gene variants influence performance in elite sprinters: a multi-cohort study. BMC Genomics. 2016 Apr 13;17:285. doi: 10.1186/s12864-016-2462-3.
PMID: 27075997

Rankinen T, Fuku N, Wolfarth B, Wang G, Sarzynski MA, Alexeev DG, Ahmetov II, Boulay MR, Cieszczyk P, Eynon N, Filipenko ML, Garton FC, Generozov EV, Govorun VM, Houweling PJ, Kawahara T, Kostryukova ES, Kulemin NA, Larin AK, Maciejewska-Karłowska A, Miyachi M, Muniesa CA, Murakami H, Ospanova EA, Padmanabhan S, Pavlenko AV, Pyankova ON, Santiago C, Sawczuk M, Scott RA, Uyba VV, Yvert T, Perusse L, Ghosh S, Rauramaa R, North KN, Lucia A, Pitsiladis Y, Bouchard C.
No Evidence of a Common DNA Variant Profile Specific to World Class Endurance Athletes. PLoS One. 2016 Jan 29;11(1):e0147330. doi: 10.1371/journal.pone.0147330. eCollection 2016.
PMID: 26824906

Pitsiladis YP, Tanaka M, Eynon N, Bouchard C, North KN, Williams AG, Collins M, Moran CN, Britton SL, Fuku N, Ashley EA, Klissouras V, Lucia A, Ahmetov II, de Geus E, Alsayrafi M; Athlome Project Consortium.
Athlome Project Consortium: a concerted effort to discover genomic and other "omic" markers of athletic performance.
Physiol Genomics. 2016 Mar;48(3):183-90. doi: 10.1152/physiolgenomics.00105.2015. Epub 2015 Dec 29. Review.
PMID: 26715623

Webborn N, Williams A, McNamee M, Bouchard C, Pitsiladis Y, Ahmetov I, Ashley E, Byrne N, Camporesi S, Collins M, Dijkstra P, Eynon N, Fuku N, Garton FC, Hoppe N, Holm S, Kaye J, Klissouras V, Lucia A, Maase K, Moran C, North KN, Pigozzi F, Wang G.
Direct-to-consumer genetic testing for predicting sports performance and talent identification: Consensus statement.
Br J Sports Med. 2015 Dec;49(23):1486-91. doi: 10.1136/bjsports-2015-095343.
PMID: 26582191