We are a major player and market leader in the consumer health & beauty industry, with a portfolio that spans multiple channels, demographics and categories. We are seeking a preclinical/in vitro screening system/model to identify biological stress-mitigating natural ingredients, compounds, or botanicals.
Systemic and oxidative stress plays a major role in skin and hair health. This is primarily mediated through the body's stress response system, specifically the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. The HPA axis is a complex set of interactions between the hypothalamus, pituitary gland, and adrenal glands. When the body perceives stress, the hypothalamus releases corticotropin-releasing hormone (CRH), which signals the pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH then stimulates the adrenal glands to produce cortisol, a key stress hormone.
At the level of the hair follicle, the expression and presence of elevated cortisol can activate various signaling pathways within the hair follicle cells, leading to changes in gene expression and cellular function. Cortisol can disrupt the normal hair growth cycle, which consists of the anagen (growth), catagen (regression), and telogen (resting) phases. Elevated cortisol levels can prematurely push hair follicles into the telogen phase, a period when the hair follicle is inactive and hair is more likely to fall out. This can lead to a condition called telogen effluvium, where an excessive number of hair follicles enter the telogen phase, resulting in increased hair shedding and noticeable hair thinning.
While various Contract Research Organizations (CROs) offer biochemical and transcriptional measures to detect increased stress in the hair follicle in vitro, a deeper understanding of the larger stress pathway (HPA) would reveal how each mediator and biomarker impacts the hair follicle unit (FU). This understanding could lead to the development of in vitro models using these markers to screen for new compounds that mitigate stress effects on hair health.
We are seeking high-throughput screening system/model to identify stress-mitigating natural ingredients, compounds, or botanicals through enzymatic inhibition (11β-hydroxysteroid dehydrogenase), receptor interference, activity reduction, and/or gene expression modulation. Solutions of interest include, but are not limited to, in vitro or ex vivo screening models focusing on the options below.
- Models focusing on measurement of the activity of key enzymes involved in glucocorticoid metabolism, such as 11β-hydroxysteroid dehydrogenase
- Models focusing on gene expression changes related to stress response pathways, such as the HPA axis, unfolded protein response, & oxidative stress response
- Cell line models: HaCaT keratinocytes, dermal papilla cells, and dermal fibroblasts to measure changes in CRH, ACTH, and cortisol levels, as well as markers of inflammation, vascular function, and hair follicle stem cell quantity and viability.
- Hair follicle models: ex-vivo human hair follicle cultures to assess the impact of stress on hair follicle biology and stem cell populations.
- Higher order models: nematode C. elegans to investigate biochemical and transcriptional stress-related endpoints, such as changes in CRH, ACTH levels, DHS-30 (7β-hydroxysteroid dehydrogenase) activity, as well as physiological stress endpoints, including lifespan, thermotolerance, and resistance to oxidative stress.
- Models focusing on monitoring levels of stress-related metabolites like cortisol, cortisone, & their precursors &metabolites.
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Model(s) capable of high throughput screening for the effect of botanicals or pharmaceuticals in stress response, via in vitro or cell-based systems, measuring either hormonal release or changes in gene expression (transcriptional).
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Model(s) must be capable of screening a wide variety of chemicals, extracts, etc.
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Provide a high-level experimental plan with timelines to outline your approach/key milestones.
- Validated model(s)
- Demonstrated reproducibility
- Higher throughput in nature (ability to screen more than 20 materials at a time)
- High sensitivity (ideal)
- Time effective - ability to deliver results through testing ingredients in the platform by the end of 2024.
- No animal nor animal-derived models or systems with the exception of C. elegans.
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