Difference between revisions of "Team:Queens Canada/Description"

Line 20: Line 20:
 
<div class="column full_size">
 
<div class="column full_size">
 
<h2>In The Glow: Luminescent Biosensors for Hormone Detection and Diagnosis</h2>
 
<h2>In The Glow: Luminescent Biosensors for Hormone Detection and Diagnosis</h2>
<h3>Background</h3>
+
<h3>Overview</h3>
  
  
 
<div class="column full_size">
 
<div class="column full_size">
<h3>Biosensors</h3>
+
<p>The human endocrine system is responsible for keeping the body in a delicate balance by controlling essential functions such as thermoregulation, awareness, thirst, satiety,  sexual drive, as well as behaviours. The body uses chemical messengers called hormones to maintain this delicate balance, by signaling to the cells throughout your body on how to behave. Examples of hormones include Estrogen, Testosterone, Oxytocin, and Cortisol. This years our team sought to produce engineered protein biological sensors for the detection and quantification of hormones present in saliva as a diagnostic tool for hormone disorders, treatment monitoring, and as general a tool for monitoring endocrine function. As a starting point for our biological sensors we have focused on detection of the steroid hormone cortisol.
<p>Biosensors are devices that are able to detect the presence of analytes and effectively convert this biological response to an electrical signal. This system consists of three components: a bioreceptor, transducer and detector. The bioreceptor is able to form substrate-specific interactions with the analyte. The transducer is then able to detect the substrate-receptor interaction and transmit this into an electrical signal, which is amplified and processed by the detector. This information is then capable of being sent to a data storage device for quantification and analytical purposes. </p>
+
  
UPDATE THIS IMAGE PLEASE!
+
We have taken two approaches to the biologic sensors for the measurement of Cortisol. Firstly, we have constructed a glucocorticoid sensor utilizing changes in Fluorescence Resonance Energy Transfer (FRET) to detect hormones. Secondly, we have began developing a novel biological sensor which utilizes intein splicing, producing a signal for hormone quantification.
<img src=" />
+
 
 +
In addition to our work in the laboratory, we developed complimentary hardware and software, which we aim to incorporated into the form of diagnostic pacifier device with a built in luminometer, allowing for portable, quick, and non-invasive collection, and measurement of salivary analytes in infants.
 +
</p>
 
</div>
 
</div>
  
 
<div class="column full_size">
 
<div class="column full_size">
<h3>Ligand Binding Domain</h3>
+
<h3>Why Cortisol?</h3>
<p>Nuclear receptors are a family of evolutionarily conserved proteins that functions as a ligand-dependent transcription factor [1]. After binding certain ligands, the receptor undergoes a conformational change which activates them, and allows them to bind directly to DNA to alter gene transcription [1]. Circulating steroid hormones, like cortisol, are able to activate the receptor and mediate processes such as stress response, energy metabolism and immune responses [2]. The ligand binding domain of nuclear receptors generally consists of eleven alpha-helices and two beta-sheets that enable the formation of a three-layered protein structure [2]. There also exists a regulatory C-terminal helix, titled "helix 12”, that is essential for hormone binding. There are conserved residues within these helices which form critical interactions with the ligand allowing for specificity within the interaction [2].  
+
<p>Cortisol is a steroid hormone that is made in the cortex of the adrenal glands. It is released in the bloodstream, and is transported all around the body, regulating many bodily functions. Cortisol is often titled “the stress hormone” as it associated with response to stressful stimuli and is released as part of the bodies “flight or fight response”. Normally, Cortisol levels follow a diurnal rhythm meaning, they’re elevated immediately when one wakes up and decrease throughout the day. Fluctuating cortisol levels that differ from the diurnal rhythm can serve as an indicator of various disorders. Thus, cortisol can be a very useful biomarker of health and wellness.
<br><em>Although our team is starting with the glucocorticoid receptor, the homology in steroid hormone receptors allows for the potential ability to exchange receptor types in order to quantify a vast array of different analytes. Both of the detection methods we have developed utilize conformational changes in the nuclear receptor ligand binding domain to produce a measurable signal.</em></p>
+
        Some functions regulated by  cortisol include the regulation of blood sugar levels, metabolism, cardiovascular health, controlling inflammation and immune function1. Since cortisol enhances the production of glucose from the liver through gluconeogenesis and counterbalances the effects of insulin,1 it can potentially be used as a biomarker for conditions like hypoglycemia (low blood sugar) and insulinemia (abnormally elevated blood-insulin levels). In terms of metabolism, cortisol is an overall catabolic hormone which decreases lean body mass, muscle mass, and can increase energy expenditure.2 As elevated cortisol production and altered local regulation are associated with obesity,3 further research on cortisol may serve beneficial in combatting this prevalent condition. Cortisol measurements can also assist in early diagnosis of metabolic disorders such as Cushing’s syndrome and Addison’s disease, which are caused by hyper and hypo-secretion of cortisol, respectively. Symptoms of Cushing’s Syndrome include obesity, bone loss, and high blood pressure. Conversely, the symptomatology of Addison's Disease include weight loss, muscle/joint pains, and low blood pressure.
 +
Presently, the most common method of measuring cortisol levels is through blood work. Other methods however, such as salivary tests, are generating interest as they are far less invasive and easier for sample collection. One key difference between blood and saliva tests for hormones is that salivary tests are able to measure the amount of free, unbound hormone that is available to act on a given tissue. Since 95-99% of steroid hormones flowing in the blood are bound by carrier proteins, blood tests may give a less accurate representation of how much hormone is available to target tissues.4
 +
The effects of abnormal cortisol levels constitute a wide variety of unpleasant symptoms. Effective and frequent monitoring of this hormone can allow for early diagnosis of disease, improved treatment, treatment monitoring, and quantifiable tracking of well-being. Using saliva as a diagnostic method for cortisol abnormalities has great potential as it is non-invasive, accessible and self-administrable, meaning the general population might be more inclined for regular tests.
 +
</p>
 
</div>
 
</div>
  
<div class="column full_size">
 
<h3>Approaches</h3>
 
<p> Starting with the natural Ligand Binding Domain of nuclear receptors as our means of binding to ligands, we took two approaches to producing a measurable signal from this interaction.
 
  
<br><em>Please click here to see our approaches and design process</em></p>
+
<div class="column half_size">
 +
<h4>References</h4>
 +
<ol id="noIndent">
 +
<li><a href="McKay LI, Cidlowski JA. Physiologic and Pharmacologic Effects of Corticosteroids. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003. Available from:  https://www.ncbi.nlm.nih.gov/books/NBK13780/</a></li>
 +
<li><a href="Effects of Cortisol on Carbohydrate, Lipid, and Protein Metabolism: Studies of Acute Cortisol Withdrawal in Adrenocortical Failure. Christiansen J, Djurhuus C, Gravholt C, Iversen P Christiansen J et. al. The Journal of Clinical Endocrinology & Metabolism 2007 vol: 92 (9) pp: 3553-3559
 +
</a></li>
 +
<li><a href="Cortisol dysregulation in obesity-related metabolic disorders. Baudrand R, Vaidya A. Current opinion in endocrinology, diabetes, and obesity. 2015 vol: 22 (3) pp: 143-9</a></li>
 +
<li><a href="Lewis JG. Steroid analysis in saliva: An overview. Clin Biochem Rev.  2006;27(3):139-146./</a></li>
 +
</ol>
  
  

Revision as of 21:20, 8 September 2018

In The Glow: Luminescent Biosensors for Hormone Detection and Diagnosis

Overview

The human endocrine system is responsible for keeping the body in a delicate balance by controlling essential functions such as thermoregulation, awareness, thirst, satiety, sexual drive, as well as behaviours. The body uses chemical messengers called hormones to maintain this delicate balance, by signaling to the cells throughout your body on how to behave. Examples of hormones include Estrogen, Testosterone, Oxytocin, and Cortisol. This years our team sought to produce engineered protein biological sensors for the detection and quantification of hormones present in saliva as a diagnostic tool for hormone disorders, treatment monitoring, and as general a tool for monitoring endocrine function. As a starting point for our biological sensors we have focused on detection of the steroid hormone cortisol. We have taken two approaches to the biologic sensors for the measurement of Cortisol. Firstly, we have constructed a glucocorticoid sensor utilizing changes in Fluorescence Resonance Energy Transfer (FRET) to detect hormones. Secondly, we have began developing a novel biological sensor which utilizes intein splicing, producing a signal for hormone quantification. In addition to our work in the laboratory, we developed complimentary hardware and software, which we aim to incorporated into the form of diagnostic pacifier device with a built in luminometer, allowing for portable, quick, and non-invasive collection, and measurement of salivary analytes in infants.

Why Cortisol?

Cortisol is a steroid hormone that is made in the cortex of the adrenal glands. It is released in the bloodstream, and is transported all around the body, regulating many bodily functions. Cortisol is often titled “the stress hormone” as it associated with response to stressful stimuli and is released as part of the bodies “flight or fight response”. Normally, Cortisol levels follow a diurnal rhythm meaning, they’re elevated immediately when one wakes up and decrease throughout the day. Fluctuating cortisol levels that differ from the diurnal rhythm can serve as an indicator of various disorders. Thus, cortisol can be a very useful biomarker of health and wellness. Some functions regulated by cortisol include the regulation of blood sugar levels, metabolism, cardiovascular health, controlling inflammation and immune function1. Since cortisol enhances the production of glucose from the liver through gluconeogenesis and counterbalances the effects of insulin,1 it can potentially be used as a biomarker for conditions like hypoglycemia (low blood sugar) and insulinemia (abnormally elevated blood-insulin levels). In terms of metabolism, cortisol is an overall catabolic hormone which decreases lean body mass, muscle mass, and can increase energy expenditure.2 As elevated cortisol production and altered local regulation are associated with obesity,3 further research on cortisol may serve beneficial in combatting this prevalent condition. Cortisol measurements can also assist in early diagnosis of metabolic disorders such as Cushing’s syndrome and Addison’s disease, which are caused by hyper and hypo-secretion of cortisol, respectively. Symptoms of Cushing’s Syndrome include obesity, bone loss, and high blood pressure. Conversely, the symptomatology of Addison's Disease include weight loss, muscle/joint pains, and low blood pressure. Presently, the most common method of measuring cortisol levels is through blood work. Other methods however, such as salivary tests, are generating interest as they are far less invasive and easier for sample collection. One key difference between blood and saliva tests for hormones is that salivary tests are able to measure the amount of free, unbound hormone that is available to act on a given tissue. Since 95-99% of steroid hormones flowing in the blood are bound by carrier proteins, blood tests may give a less accurate representation of how much hormone is available to target tissues.4 The effects of abnormal cortisol levels constitute a wide variety of unpleasant symptoms. Effective and frequent monitoring of this hormone can allow for early diagnosis of disease, improved treatment, treatment monitoring, and quantifiable tracking of well-being. Using saliva as a diagnostic method for cortisol abnormalities has great potential as it is non-invasive, accessible and self-administrable, meaning the general population might be more inclined for regular tests.

References