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Research Day 2007

2007 Research Day Schedule (pdf)

Jessica Scott

 

THE EFFECTS OF PROLONGED STRENUOUS EXERCISE ON BETA RECEPTOR RESPONSIVENESS IN MALE AND FEMALE TRIATHLETES

Meaghan MacNutt

  WHITE MOUNTAIN 2007 – THE HIP AND GRIP LABS GET HYPOXAEMIC

Cynthia Thomson

 

THE RELATIONSHIP BETWEEN GENETICS AND SKIING/SNOWBOARDING BEHAVIOURS: VARIANTS IN THE DOPAMINE RECEPTOR GENE

Paul Gallant

 

EATING DISORDERS IN MEN

Tony Carlsen

 

PERCEPTUAL PROCESSING TIME DIFFERENCES DUE TO VISUAL FIELD ASYMMETRIES

Adam Campbell

 

TRACE CONDITIONING OF AUTOMATIC POSTURAL REFLEXES

Justin Davis

 

STIFFENING STRATEGY MAINTAINED AT EXTREME SURFACE HEIGHTS

Catherine Chan

 

TREADMILL TRAINING AND LEG RESISTANCE DURING SWING PHASE: A PRELIMINARY REPORT

Pei Wang

 

COMMON HAPLOTYPES IN THE BETA-2 ADRENERGIC RECEPTOR GENE ARE NOT ASSOCIATED WITH ACUTE MOUNTAIN SICKNESS (AMS) SUSCEPTIBILITY IN NEPALESE

Kathryn Luttman

 

EFFECT OF THE HEMIPARETIC GAIT PATTERN ON TURNING

Clare Cayley

 

COPING WITH AN INTERPERSONAL STRESS IN FEMALE ADOLESCENT TEAM SPORT

Katie Morton

 

TRANSFORMATIONAL TEACHING AND PHYSICAL ACTIVITY BEHAVIOURS

Matthew Fedoruk

 

DEVELOPMENT OF A PROTOTYPE BLOOD-BASED TEST FOR EXOGENOUS ERYTHROPOIETIN ACTIVITY BASED ON TRANSCRIPTIONAL PROFILING

Jessica Scott - THE EFFECTS OF PROLONGED STRENUOUS EXERCISE ON BETA RECEPTOR RESPONSIVENESS IN MALE AND FEMALE TRIATHLETES

Gender differences in neuroendocrine and metabolic responses to prolonged strenuous exercise (PSE) have been well documented. The aim of this investigation was to examine gender differences in left ventricular function and cardiac β-receptor responsiveness following a single bout of PSE. Nine male and eight female triathletes were examined during three separate sessions: before, immediately after, and 24 h following a half-ironman triathlon using dobutamine stress echocardiography. Steady-state graded infusions of dobutamine were used to assess β-receptor responsiveness. Slopes calculated from linear regressions between dobutamine doses and changes in heart rate and contractility for each participant were used as an index of β-receptor responsiveness. Despite no change in preload, fractional area change decreased from baseline after the race in both males and females, with a greater decrease in males (males: 54.1 ± 2.1 to 50.7 ± 3.4 % vs. females: 55.4 ± 2.7 to 53.3 ± 2.5 %; p<0.05). The amount of dobutamine necessary to increase HR 25 beats.min-1 (males: 29.6 ± 6.6 to 42.7 ± 12.9 μg.kg-1.min-1 vs. females: 23.5 ± 4.0 to 30.0 ± 7.8 μg.kg-1.min-1; p<0.05) and contractility 10 mmHg.cm-2 (males: 20.9 ± 5.1 to 37.0 ± 11.5 μg.kg-1.min-1 vs. females: 22.6 ± 6.4 to 30.7 ± 7.2 μg.kg-1.min-1; p<0.05) was greater in both males and females post-race. However, the amount of dobutamine required to induce these changes was greater in males, reflecting larger β-receptor alterations in male triathletes following PSE relative to females. These data suggest that following an acute bout of PSE, male triathletes demonstrate an attenuated chronotropic and inotropic response to β-adrenergic stimulation compared with female triathletes.

Meaghan MacNutt- WHITE MOUNTAIN 2007 – THE HIP AND GRIP LABS GET HYPOXAEMIC

The scientific method sounds so simple: ask a question, make a prediction, design an experiment, collect some data, and answer the question. However, we all know from experience that there’s more to research than whipping off a few experiments in the lab and crunching some numbers to support or reject a hypothesis. For almost two years, I’ve been discovering exactly what it takes to plan a large scale, expensive, multi-institutional, international collaborative field study to answer what seemed like a fairly straightforward question: does previous experience at altitude make it easier to adjust to high altitude conditions in the future? ? It has been a challenging and rewarding experience organizing a high altitude expedition to another country and scheduling the lives of sixteen individuals for seven weeks, sometimes down to the minute. I’ll share my experiences to date and discuss the scientific, logistical and politically incorrect aspects of project management.

Cynthia Thomson - THE RELATIONSHIP BETWEEN GENETICS AND SKIING/SNOWBOARDING BEHAVIOURS: VARIANTS IN THE DOPAMINE RECEPTOR GENE

PURPOSE: To determine whether an association exists between “sensation-seeking” (a personality trait) and variations within the dopamine-4-receptor gene (DRD4) in a population of skiers and snowboarders. HYPOTHESIS: Certain variants in the dopamine receptor gene (DRD4) will be over-represented in a cohort of skiers and snowboarders inclined to partake in “sensation seeking behaviours” (as defined by a standardized questionnaire, Zuckerman-Kuhlman Personality Questionnaire, and by a ski/snowboard-specific questionnaire), compared to individuals who are not so inclined. JUSTIFICATION: Previous research has shown a large genetic influence over personality traits, especially sensation seeking. The DRD4, a highly polymorphic gene encoding dopamine receptors in the brain, has been associated with sensation/novelty seeking in some, but not all studies. The inconsistencies between studies may be due to the heterogeneity in the behaviours being assessed. Many studies have looked at sensation seeking behaviour in the context of antisocial behaviour (e.g. narcotic abuse, schizophrenia). This will be the first study to address the possibility that genetics may play a role in an individual’s inclination towards “sensation seeking” in sporting context. OBJECTIVES: The objectives of this study are three-fold: 1) to determine the level of general sensation seeking for each subject using a standardized questionnaire (Zuckerman-Kuhlman Personality Questionnaire, ZKPQ 1993); 2) to determine the level of general sensation seeking specifically in the context of skiing/snowboarding behaviour using a questionnaire created for the purpose of this study by our research group, and 3) to genotype the subjects for variants in the DRD4 gene and to determine if there is an association between any of the variants in the gene and “sensation seeking” behaviour.

Paul Gallant - EATING DISORDERS IN MEN

Although it was long estimated that 10%-15% of individuals with eating disorders are male (Carlat, Camargo, & Herzog, 1997), relatively little research has been conducted in this population (Tylka & Subich, 2002). One the latest research studies published findings on men with eating disorders (Hudson & Pope, 2007) reports that the number of males to females with eating disorders is predicted to be closer to one in four. Males screened at the provincial eating disorders treatment center for adults accounted for less than 3% of individuals assessed. Recent participation in the Males Special Interest Group (SIG) at the international eating disorders conference suggests there is very little discussion of males with eating disorders despite their existence. Many research articles include no reference to males or the gender breakdown of participants in their research; further stigmatizing eating disorders as a women's only illness. Statistics suggest an increase in the number of males with eating disorders (ED). This number is likely to be substantially higher among male athletes, male models, and gay males (Hill, 2004). Unlike most women men may not ask for and accept support (Andersen, Cohn, & Holbrook, 2000, p.218) as men have been raised to conceal or disregard their emotions. Men rarely seek typical treatment for reasons that include the care being predominately oriented towards females (Birmingham & Beumont, 2004). Upcoming research will further our understanding of men with eating disorders through the use of focus groups and interviews. Recent research on quality of life findings will also be presented.

Anthony N. Carlsen, Dana Maslovat, Romeo Chua, & Ian M. Franks - PERCEPTUAL PROCESSING TIME DIFFERENCES DUE TO VISUAL FIELD ASYMMETRIES

Recent experiments (e.g. Danckert & Goodale, 2001; Kahn & Lawrence, 2005) have reported increased endpoint accuracy for movements performed in the lower visual field (LVF) vs. the upper visual field (UVF). To account for these results, it was suggested that there is superior feedback-based processing in the LVF resulting from a visuo-motor subsystem processing advantage. Specifically, an overrepresentation of the LVF in the dorsal visual pathway as well as a greater retinal ganglion cell density was implicated. However, it is not clear whether differences in the perceptual subsystem may also play a role in the LVF movement advantage. The goal of the present experiment was to investigate this possibility. Inspection time (IT) is a measurement of the stimulus duration required in order to make a perceptual judgment to some level of accuracy, and thus is thought to measure perceptual processing time (Sadler and Deary, 2001). An accumulator model (Vickers, 1970) suggests that as more time is available to inspect the stimulus, more information is passed into the perceptual system. In the present experiment, participants identified which leg of an asymmetrical “pi” figure was longer. After fixating on a central cross, the stimulus appeared in either the central visual field, the UVF or the LVF for a brief period (10 conditions between 16.6 ms and 166 ms) before being backward masked. Significant main effects were found in percentage of correct identification for both visual field and duration, as well as a significant interaction between these factors. These results indicate that IT was shortest for central vision. However, differences were also observed between the LVF and UVF, with more correct identifications in the LVF at shorter stimulus durations. This supports the suggestion that more information was available in the LVF, leading to more correct identifications, and may indicate that at least part of the LVF movement advantage may be due to perceptual factors.

A.D. Campbell1, C. Dakin1, M.G. Carpenter - TRACE CONDITIONING OF AUTOMATIC POSTURAL REFLEXES

Introduction: Classical conditioning has been used to elicit specific muscular responses to numerous forms of external stimuli. Trace conditioning, whereby the conditioned stimulus (CS) is separated from the unconditioned stimulus (US) by a short-latency ‘off-stimulus’ period, has been shown to develop robust associations in initiating the eye-blink reflex to an auditory tone [1]. Automatic postural reflexes (APRs) are thought to be longer-loop reflexes that elicit stereotypical postural responses to unexpected balance perturbations. The aim of the present research project is to determine whether a conditioned auditory stimulus can be used to elicit an APR in the absence of any visual, somato-sensory, or vestibular stimuli. Methods: Nine healthy young adults (age range: 22-26 years) volunteered for this study. With their eyes closed, subjects experienced 17 toe-up rotational perturbations (US) of 7.5o at 60o/sec presented with a random 5-60s inter-stimulus interval. Rotational perturbations were coupled with a preceding 200ms auditory tone (CS) ending 100ms before the onset of the US. After the 17 conditioning trials, subjects were exposed to a final trial consisting of only the CS (i.e. tone without a subsequent perturbation). Surface electromyography (EMG) was recorded unilaterally in the tibialis anterior (TA) and the soleous (SOL) muscles. Onset latencies were identified as the time when muscle activity surpassed two standard deviations above mean background activity calculated 100ms prior to the CS. Muscle onsets were referenced to the start of platform movements specific to each trial. Results: After the series of CS-US conditioning trials, seven subjects (78%) displayed clear TA responses to the presentation of the CS-only. Mean onset latencies of TA during conditioning trials (136.38±55.53ms) were not significantly different than latencies of TA onsets during CS-only trials [t(6)=1.88, p>0.10, non-directional]. Interestingly, although clear stretch reflex activity was evident in SOL during conditioning trials, no stretch reflex activity was observed in SOL when the CS was presented alone. Discussion: The results from this project demonstrate the feasibility of using trace conditioning to elicit an APR from an auditory stimulus. This conditioning response is evident in subjects’ TA reaction to the auditory tone in the absence of physical perturbation. We believe that because TA response latencies are similar to those seen during balance perturbing trials, supraspinal influences may have a role in reflexive balance response initiation in the absence of a proprioceptive mechanism. Furthermore, absent SOL responses to CS-only presentations suggests that lower leg stretch reflexes are not a contributing factor in triggering APRs. References [1] Steinmetz JE (2000) Brain substrates of classical eyeblink conditioning: a highly localized but also distributed system. Behav Brain Res 110:13-24

J.R. Davis1, M.G. Carpenter1 and A.L. Adkin2. - STIFFENING STRATEGY MAINTAINED AT EXTREME SURFACE HEIGHTS

Research Institute for Aging, Brock University, Canada Introduction: Postural anxiety manipulated through changes in surface elevation has been shown to significantly influence the control of upright stance (1). When full vision was available, subjects adopted a stiffening strategy when standing at elevated surface heights up to 1.6m. (1). However, conflicting results have been reported when subjects stood at more extreme heights and when peripheral vision was removed (4,5). Therefore the purpose of this study is to investigate how standing at increased surface heights higher than 1.6m and under reduced peripheral vision affect centre of pressure (COP) displacements during quiet stance. Methods: 8 healthy subjects, (4 male; age range 22-30 years) stood quietly on a force plate for one minute durations while elevated from ground level to 0.75m, 1.6m and 3.2m using a hydraulic lift. Three visual conditions were counter balanced at each height: eyes open, eyes closed and while wearing blinders designed to occlude peripheral vision. COP was calculated offline from force plate data (100Hz; 5 Hz low pass filtered) from which RMS amplitude and MPF were derived in anterior-posterior (A-P) and medial-lateral (M-L) directions. At each height under each visual condition subjects’ perceived levels of anxiety and confidence were gauged using task specific self-rated questionnaires (1). Results: COP measures were significantly influenced by postural anxiety. Independent of visual condition, MPF was significantly influenced by surface height in both the A-P (F(3,21)=8.5, p<0.001) and M-L (F(3,21)=8.8, p<0.001) directions. On average, MPF increased by 57% in the A-P and 35% in the M-L directions when subjects were standing at 3.2m compared to ground level. Although not statistically significant, RMS amplitude tended to decrease with increased surface height in the eyes open condition. On average RMS decreased when subjects were standing at 3.2m compared to ground level by 16% and 13% in the A-P and M-L directions respectively. Discussion: With increasing heights, subjects adopted a stiffening strategy characterized by higher frequency and lower amplitude COP displacements. These observations contrast reports by Nakahara et al. (2000) and Simeneov and Hsiao (2001) of larger COP displacements at elevations above 3m. Furthermore, altering the amount of peripheral visual input subjects received did not affect COP displacements at higher heights suggesting that the observed changes in COP RMS and MPF were due to psychosocial influences and not height dependent changes in the field of vision. Carpenter et al. 1999. Surface height effects on postural control: A hypothesis for a stiffness strategy for stance. J Ves Res 9: 277-286 Nakahara et al. 2000. Influence of height on the spatial orientation and equilibrium of the body. Head Neck Surg. 123:501-504 Simeonov and Hsiao. 2001. Height, surface firmness, and visual reference effects on balance control. Inj prev 7: (Suppl 1) 50-53

Catherine Chan - TREADMILL TRAINING AND LEG RESISTANCE DURING SWING PHASE: A PRELIMINARY REPORT

Introduction: There is increasing interest in task-specific treadmill training strategies for the recovery of walking function following neurological injury, such as spinal cord injury (SCI) or stroke. Such task-specific strategies are thought to improve gait function by providing appropriate sensory cues associated with stepping. However, we believe that current treadmill training strategies do little to facilitate flexor muscle activity because the limb is often assisted during swing. Indeed, deficits in swing phase activity require many people to rely on external devices or have limited gait function. Therefore, the objective of this study is to investigate the feasibility of combining treadmill training with resisting the limb during the swing phase in people with neurological injury. Methods: Ambulatory subjects with chronic stroke or incomplete SCI were recruited to participate in this pilot investigation. Body-weight supported treadmill training combined with resisting of the leg during the swing phase was administered for a total of 12 30-minute sessions (2 to 3 times a week). Swing phase resistance was achieved by the addition of small weights (5% of body weight) wrapped around the lower leg. Surface electromyography and functional ambulation measures (10-meter walk test) were recorded before and after training and perceived level of exertion was recorded during training. Results: Walking with additional weight around the leg resulted in enhanced flexor muscle activity during swing. The treadmill training sessions were well-tolerated. Following 12 sessions of training, subjects showed an improvement in functional ambulation measures. Conclusions: The results show that flexor muscle activity during swing is influenced by proprioceptive disturbances in subjects with neurological injury. Further studies are needed to determine whether treadmill training combined with swing phase resistance confers further benefits above treadmill training alone.

Pei Wang - COMMON HAPLOTYPES IN THE BETA-2 ADRENERGIC RECEPTOR GENE ARE NOT ASSOCIATED WITH ACUTE MOUNTAIN SICKNESS (AMS) SUSCEPTIBILITY IN NEPALESE

Purpose: The beta-2 adrenergic receptor (2AR) is the principal catecholamine receptor in the lung and mediates responses to the improved O2 delivery during altitude acclimatization. In this study, we applied a new way of genetic analysis named as haplotype analysis to investigate the association between gene variants and acute mountain sickness. Methods: We used HapMap (http://www.hapmap.org/whatishapmap.html) which is the database of an international project and contains the latest haplotype data of human genome. Seven tag-variants in the gene that encodes the 2AR were chosen from HapMap. We genotyped these variants in a cohort of individuals with, or without, AMS who were ascertained at the Janai Purnima Festival at Lake Gosain Kunda, Nepal (4380 meters). Results: No significant differences in genotype or allele frequencies were observed between AMS and non-AMS group for any of the tag-variants. Conclusion: This study represents the first application of the powerful HapMap database to understanding the genetic basis of altitude sickness. None of the variants were associated with acute mountain sickness (either clinically diagnosed or based on a Lake Louise score of >3) suggesting that none of the variants close to, or in, the gene encoding the 2 adrenergic receptor play a role in the etiology of the condition (although the relatively small size of our sample limits the power to exclude small effects).

Kathryn Luttman, Catherine Chan, Tania Lam - EFFECT OF THE HEMIPARETIC GAIT PATTERN ON TURNING

Introduction: Everyday situations require a broad range of walking abilities, including turning corners and maneuvering around objects. However, gait rehabilitation after stroke tends to focus on straight-ahead walking. To enhance functional ambulation after stroke, more information is needed about how people with stroke perform in different walking conditions. The first purpose of this study was to determine if people with stroke have more difficulty turning than controls. Second, we investigated gait asymmetry during turns. Normally, more time is spent on the inside leg of the turn, compared to the outside leg. Does the inherent asymmetry in the hemiparetic gait impact turning performance in people with stroke? Our second purpose, therefore, was to describe how people with stroke adjust their gait pattern during turning. Methods: Purpose 1- Turning Performance: 3 stroke and 7 control subjects walked along paths outlined on the floor with tape requiring 45º, 90º and 180º turns. Time and number of steps required to turn were discerned from videotape, and compared between subject groups and between walking conditions. Purpose 2- Gait Asymmetry: 6 stroke and 8 control subjects walked along circular paths of 0.5, 1.0. and 2.0 m radii. Force sensitive resistors (FSR) placed under the heel and lateral and medial metatarsal of both feet. FSR signals were used to determine the single-support (SS) time of each leg, as well as to estimate the ground reaction force (GRF). Gait asymmetry in SStime and SSGRF was compared between subject groups and between walking conditions. Results: Purpose 1: Compared to controls, stroke subjects took more time and more steps to complete turns, in all conditions. There did not appear to be a difference between turns towards the paretic vs. non-paretic side. Purpose 2: Control subjects had longer SStime on the inside leg while turning, as compared with straight walking, with more pronounced asymmetry in tighter circles. Stroke subjects did not tend to modulate SStime when turning towards the paretic leg. For turning toward the non-paretic leg, modulation of SStime appeared similar to controls. There did not appear to be modulation of SSGRF in either controls or stroke subjects. Conclusion: To date, there has been very little research on turning in stroke. These results indicate that people with stroke have difficulty turning, which may be related to difficulty spending time on the paretic leg. Additional studies are required to fully understand the neural and biomechanical factors that limit turning in people with stroke.

Clare Cayley - COPING WITH AN INTERPERSONAL STRESS IN FEMALE ADOLESCENT TEAM SPORT

Stress in sport is complex and can lead to a number of undesirable consequences such as burnout, performance difficulties, interpersonal problems, and injury. There are many ways to conceptualize sport related stress. One model that has been popular is Lazarus’s (1984, 1999) Cognitive-Motivational-Relational model that holds that stress is best understood as a transactional relationship between a person and their environment. Various stress relationships occur when the person evaluates (appraises) a transaction as taxing or exceeding personal resources and potentially endangering his or her well-being. Two key processes influences stress; appraisal and coping. Appraisal processes are influenced by personal factors (personality, goals, personal resources) as well as environmental demands and the availability of external resources (such as social support). Coping can be understood as a self-regulating mechanism that involves constantly changing cognitive and behavioural efforts to manage the perceived external and internal demands of a stressful situation (Lazarus & Folkman, 1984). The study of stress and coping in sport has been somewhat limited by researchers inability to control the type of stressor reported by the participant. In many studies athletes have reported various competitive and social stressors. Therefore, it is difficult to determine if individual differences in coping are due to differences in personal and external resources or due to differences in the stressor demands. Therefore, this study will try to control the stressor by presenting a hypothetical interpersonal stressor. Thus differences in coping should reflect individual differences in key predictor variables such as personality, appraisal, and social support. Using this hypothetical interpersonal stress scenario, I will examine how trait social anxiety will influence appraisal of threat and subsequent coping functions. However, the study will also examine how the availability of social support from team-mates can moderate the stress process. It is believed that social support can buffer and reduce stress by changing both appraisal and enhancing coping options. We will recruit approximately 200 female high school soccer players from the Greater Vancouver area. The athletes will first fill out two questionnaires designed to measure social anxiety (Interaction Anxiousness Scale; Leary, 1983) and perceived social support from team-mates (Social Provisions Scale; Weiss, 1974). The athletes will then each read a scenario describing a hypothetical interpersonal stress situation on a team. They will then indicate their perception of stress (Stress Thermometer; Kowalski & Crocker, 2001) and appraisal of threat (Stress Appraisal Measure; Peacock & Wong, 1990) based on their reaction to this scenario. We will then ask them to indicate how they think they would cope (Coping Functions Questionnaire; Kowalski & Crocker, 2001).

Katie Morton - TRANSFORMATIONAL TEACHING AND PHYSICAL ACTIVITY BEHAVIOURS

The World Health Organization (2003) estimates that across the world 60% of people do not participate in sufficient levels of physical activity in order to gain necessary health-related benefits. Not only is this physical inactivity to be found across cultures and continents (World Health Organization, 2002) but it also appears to increase during childhood and into adolescence and adulthood (Sallis & Patrick, 1994). This picture is particularly evident in Canada with over 50% of teenagers believed to lead sedentary lifestyles (Craig & Cameron, 2004). An influential context in which physical activity can be nurtured is physical education within schools (Standage, Duda, Ntoumanis, 2003). In British Columbia, all children are required to undertake physical education as part of the core curriculum, and children are potentially exposed to a range of activities that can be pursued outside of the school environment (e.g., recreational exercise, competitive sport). The overall purpose of our proposed research centres on applying a novel model of leadership that has yet to be considered within physical activity contexts, with a view to fostering exercise adoption and maintenance amongst school children. From the field of organizational psychology, Bass and Avolio (1994) conceptualized a model of transformational-transactional leadership to explain how leaders might bring about different levels of outcomes amongst their followers. This model suggests that greater effort, persistence and motivation amongst followers can be achieved by augmenting transactional methods with transformational behaviours (Bass, 1998). As it relates to the context of physical education, the key question remains as to the extent to which transformational teaching might be predictive of positive cognitions (e.g., confidence, attributions), emotions (e.g., satisfaction, well-being), and behaviours (e.g., adherence, citizenship) amongst adolescents and children. The first phase of this project is focusing on the use of qualitative methodologies to conceptualize transformational-transactional leadership in physical education, as the model developed by Bass & Avolio (1994) will need to take into account the range of behaviours that exist specifically in physical education contexts. This involves focus groups and interviews with pupils in grades 8-10 and also physical education teachers, talking “in their own words” about how teachers teach using transformational and transactional methods. Utilizing both inductive and deductive coding techniques (Miles and Huberman, 1994), the main aim of this present phase is to develop a battery of items to be used in a questionnaire that will successfully measure pupil’s perceptions of their physical education teacher’s transformational-transactional leadership behaviours. This questionnaire will be subsequently used to investigate how the behaviours and attitudes of physical education teacher’s affect pupil’s self-efficacy, self-determination and most importantly their physical activity adherence out of school. Future directions and implications are discussed.

Matthew N. Fedoruk, Don C. McKenzie, and Jim L. Rupert - DEVELOPMENT OF A PROTOTYPE BLOOD-BASED TEST FOR EXOGENOUS ERYTHROPOIETIN ACTIVITY BASED ON TRANSCRIPTIONAL PROFILING

Erythropoietin (Epo) is a naturally occurring hormone that stimulates red blood cell development. Synthetic Epo (such as recombinant human Epo, rhEpo), which is frequently to treat anaemia, is one of the most commonly prescribed drugs in the world. Unfortunately, rhEpo is also one of the most common doping agents used by endurance athletes to boost their aerobic capacity. Treating anaemia with rhEpo injections is costly and gene therapy, in which the gene encoding Epo is inserted into the individual and stimulated to produce the hormone, is a promising alternative. Unfortunately, while gene therapy has the potential to revolutionize medicine, many experts believe that illicit application of this technology will be the next major challenge to anti-doping authorities. Epo produced within the athlete by an exogenous gene would likely be identical to the natural hormone and undetectable by current tests; however, the biological pathway of which Epo is part (the response to hypoxia) is complex and involves the coordinate regulation of genes in a variety of distinct, but related pathways. Selectively stimulating only the Epo pathway would not have the same system-wide effects as the natural stimulation of entire hypoxia pathway and we predict that distinguishing between the augmented and the natural Epo responses would be possible by comparing patterns of gene expression (the “transcriptional profile”). In stage one of this project, we are using Serial Analysis Gene Expression (SAGE) to generate high-resolution transcriptional profiles of blood cells taken from mice exposed to either normobaric hypoxia (~14% O2) or rhEpo injection. We hypothesize that comparing these profiles will identify patterns of gene expression that are characteristic of Epo functioning independently of the normal hypoxia response. Once candidate genes have been identified in the mouse model, we will locate and characterize their human homologues, and incorporate the latter into blood-based test for diagnostic patterns of gene expression characteristic of exogenous Epo use. This test should work for any artificial induction or erythropoiesis, including Epo gene therapy.

 

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Last reviewed 29-May-2008

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