Understanding cellular and mitochondrial protection via topical application of antioxidants

Lead Research Organisation: Newcastle University
Department Name: Institute of Cellular Medicine

Abstract

In this PhD we will study the field of oxidative stress and bioenergetics with a focus on the skin and damage to mitochondria which is a key marker of cell ageing, given the compromised ability of mitochondria to repair themselves. Therefore research into their protection against the environment has far reaching implications in a wide variety of fields from cosmetics to pharmaceutics, along with the ability to demonstrate synergistic benefits between ingredients. This links with bioscience for Health and bioenergy.
We will study the mechanisms by which topically applied antioxidants can reduce cellular oxidative stress on mitochondria in skin. The work will include developing 3D skin models to enable the location and mode of action of the antioxidant species to be researched. Novel methods for visualising this reduction in oxidative stress will also be studied. Potential applications include novel cosmetic and drug products, along with synergistic benefits.
This is a multi-disciplinary PhD studentship and includes cellular and molecular biological techniques such as cell culture, electrochemistry, UVR dosing regimes, real time PCR, gene array profiling, mutational analysis, percutaneous absorption, bio-imaging, FACS analysis and mitochondrial functional analysis. The supervisory team will be led by Professor Birch-Machin

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/N503769/1 01/10/2015 30/09/2019
1668294 Studentship BB/N503769/1 01/10/2015 30/09/2019 Rebecca Louise Hanna
 
Description Over-the-counter moisturisers help the population with their skin dryness, redness and irritation. These symptoms typically present with compromised skin barrier integrity, increasing susceptibility to environmental stressors (e.g. sunlight and pollution) which drive their severity. In this work I created an assay to detect environmental damage to the mitochondrial DNA within cells, which was published as a method paper for others to use. A method to detect damage means that I could screen commercial ingredients for their ability to protect against it. In addition, in order to test these ingredients within creams for topical application to skin, this PhD worked on the development of a highly representative 3D human skin equivalent model which can be used to enhance product development and understanding. In collaboration with GSK I was provided with some antioxidants of interest, and the data obtained positively contributed to the existing literature that indicates these ingredients could contribute anti-inflammatory, anticarcinogenic and antioxidant properties to a product range.
Exploitation Route Portions of this work resulted in two peer-reviewed publications:
• Hanna, R., Crowther, J.M., Bulsara, P.A., Wang, X., Moore, D.J. and Birch-Machin, M.A. (2019) 'Optimised detection of mitochondrial DNA strand breaks', Mitochondrion. 46, pp.172-178.
• Naidoo, K., Hanna, R. and BirchMachin Mark, A. (2018) 'What is the role of mitochondrial dysfunction in skin photoaging?', Experimental Dermatology, 27(2), pp. 124-128

This PhD was highly technical in nature, and developed numerous scientific protocols for many different assays and model systems. This is a highly valuable resource for other researchers, as it will help them to generate ideas and ensure the efficient use of time and resources.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology,Retail

 
Description The information surrounding the antioxidants tested for GSK will guide the internal development of their skincare product range.
First Year Of Impact 2018
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Title mitochondrial DNA damage 
Description Intrinsic and extrinsic factors that induce cellular oxidative stress damage tissue integrity and promote ageing, resulting in accumulative strand breaks to the mitochondrial DNA (mtDNA) genome. Limited repair mechanisms and close proximity to superoxide generation make mtDNA a prominent biomarker of oxidative damage. Using human DNA we describe an optimised long-range qPCR methodology that sensitively detects mtDNA strand breaks relative to a suite of short mitochondrial and nuclear DNA housekeeping amplicons, which control for any variation in mtDNA copy number. An application is demonstrated by detecting 16-36-fold mtDNA damage in human skin cells induced by hydrogen peroxide and solar simulated radiation. 
Type Of Material Biological samples 
Year Produced 2018 
Provided To Others? Yes  
Impact Scaling down this assay means that small clinical samples can be used, providing a measurable outcome from non-invasive or fresh/frozen human tissue samples. Having more assays that can be used on human samples, means animal models aren't required. It is a biologically driven assay with a wide range of applications, that can detect damage and measure protection against that damage. 
URL https://www.sciencedirect.com/science/article/pii/S1567724917303458?via%3Dihub
 
Description PhD CASE award with GlaxoSmithKline Consumer Healthcare 
Organisation GlaxoSmithKline (GSK)
Department GlaxoSmithKline Consumer Health Care
Country United Kingdom 
Sector Private 
PI Contribution Confidential
Collaborator Contribution Confidential
Impact Confidential
Start Year 2016