Matiss Ozols

Wellcome Sanger Institute · Human Genetics Programme

The extracellular matrices (ECMs) of mammalian tissues play important roles in mediating and maintaining tissue function. However, aberrant and progressive remodelling of ECM components is a key feature in the pathology and ageing of many organs, including skin. Crucially, these degradative processes not only impair function, but may also release p...

During ageing, the glomerular and tubular basement membranes (BM) of the kidney undergo a progressive decline in function that is underpinned by histological changes, including glomerulosclerosis and tubular interstitial fibrosis and atrophy. This BM-specific ageing is thought to result from damage accumulation to long-lived extracellular matrix (E...

The exogenous application of small peptides can beneficially affect clinical skin appearance (wrinkles) and architecture (collagen and elastic fibre deposition and epidermal thickness). However, the discovery of new bioactive peptides has not been underpinned by any guiding hypothesis. As endogenous extracellular matrix (ECM)-derived peptides produ...

The paper’s main contributions are twofold: to demonstrate how to apply the general European Union’s High-Level Expert Group’s (EU HLEG) guidelines for trustworthy AI in practice for the domain of healthcare; and to investigate the research question of what does “trustworthy AI” mean at the time of the COVID-19 pandemic. To this end, we present the...

Extracellular matrix (ECM) in the intervertebral disc (IVD), lung and artery are thought to undergo the age-dependant accumulation of damage by chronic exposure to mechanisms such as reactive oxygen species, proteases and glycation. It is unknown whether this damage accumulation is species-dependant (via differing lifespans and hence cumulative exp...

Extracellular matrix (ECM) proteins confer biomechanical properties, maintain cell phenotype and mediate tissue repair (via release of sequestered cytokines and proteases). In contrast to intracellular proteomes, where proteins are monitored and replaced over short time periods, many ECM proteins function for years (decades in humans) without repla...

Proteases and protease inhibitors (P/PIs) are involved in many biological processes in human skin, yet often only specific families or related groups of P/PIs are investigated. Proteomics approaches, such as mass spectrometry, can define proteome signatures (including P/PIs) in tissues; however, they struggle to detect low-abundance proteins. To ov...

Extracellular matrix (ECM) in the intervertebral disc (IVD), lung and artery are thought to undergo the age-dependant accumulation of damage by chronic exposure to mechanisms such as reactive oxygen species, proteases and glycation. It is unknown whether this damage accumulation is species-dependant (via differing lifespans and hence cumulative exp...

In ageing tissues, long-lived extracellular matrix (ECM) proteins are susceptible to the accumulation of structural damage due to diverse mechanisms including glycation, oxidation and protease cleavage. Peptide location fingerprinting (PLF) is a new mass spectrometry (MS) analysis technique capable of identifying proteins exhibiting structural diff...

In ageing tissues, long-lived extracellular matrix (ECM) proteins are susceptible to the accumulation of structural damage due to diverse mechanisms including glycation, oxidation and protease cleavage. Peptide location fingerprinting (PLF) is a new mass spectrometry (MS) analysis technique capable of identifying proteins exhibiting structural diff...

Artificial Intelligence (AI) has the potential to greatly improve the delivery of healthcare and other services that advance population health and wellbeing. However, the use of AI in healthcare also brings potential risks that may cause unintended harm. To guide future developments in AI, the High-Level Expert Group on AI set up by the European Co...

This paper documents how an ethically aligned co-design methodology ensures trustworthiness in the early design phase of an artificial intelligence (AI) system component for healthcare. The system explains decisions made by deep learning networks analyzing images of skin lesions. The co-design of trustworthy AI developed here used a holistic approa...

Chronic UVR exposure of human skin can result in photo-ageing which manifests both externally and internally (as remodelling of skin layers including the extracellular matrix-rich dermis). However, the intermittent nature of UVR exposure over a timescale of decades combined with the longevity of many structural dermal proteins makes the identificat...

Ozols and Eckersley are equally contributing joint first authors. Although dysfunctional protein homeostasis (proteostasis) is a key factor in many age‐related diseases, the untargeted identification of structurally modified proteins remains challenging. Peptide location fingerprinting is a proteomic analysis technique capable of identifying struct...

Both protease- and reactive oxygen species (ROS)-mediated proteolysis are thought to be key effectors of tissue remodeling. We have previously shown that comparison of amino acid composition can predict the differential susceptibilities of proteins to photo-oxidation. However, predicting protein susceptibility to endogenous proteases remains challe...

Age, disease, and exposure to environmental factors can induce tissue remodelling and alterations in protein structure and abundance. In the case of human skin, ultraviolet radiation (UVR)-induced photo-ageing has a profound effect on dermal extracellular matrix (ECM) proteins. We have previously shown that ECM proteins rich in UV-chromophore amino...

Age-related changes in elastin refer to modifications such as nonenzymatic cross-linking and/ or proteolytic degradation, which adversely affect the mechanical and biochemical properties of elastin-rich tissues and organs. Elastin (in combination with other extracellular matrix components) forms elastic fibers. These structures are primarily respon...

Although dysfunctional protein homeostasis (proteostasis) is a key factor in many age-related diseases, the untargeted identification of structural modifications in proteins remains challenging. Peptide location fingerprinting is a proteomic analysis technique capable of identifying structural modification-associated differences in mass spectrometr...

In contrast to the dynamic intracellular environment, structural extracellular matrix (ECM) proteins with half-lives measured in decades, are susceptible to accumulating damage. Whilst conventional approaches suchas histology, immunohistochemistry and mass spectrometry are able to identify age- and disease-relatedchanges in protein abundance or dis...

Circadian rhythms are daily oscillations that, in mammals, are driven by both a master clock, located in the brain, and peripheral clocks in cells and tissues. Approximately 10% of the transcriptome, including extracellular matrix components, is estimated to be under circadian control. Whilst it has been established that certain collagens and extra...

In this chapter we discuss the molecular composition and structure of the epidermis, dermal-epidermal junction, dermis and hypodermis. We highlight the contribution of long-lived dermal collagens, elastic fibres, proteoglycans and hyaluronic acid to skin function and also consider the role of apparently “minor” skin components. In order to characte...

Linked Article: Badshah et al. Br J Dermatol 2019; 180:1135–1149.

Defining protein composition is a key step in understanding the function of both healthy and diseased biological systems. There is currently little consensus between existing published proteomes in tissues such as the aorta, cartilage and organs such as skin. Lack of agreement as to both the number and identity of proteins may be due to issues in p...

Although the composition and structure of cartilaginous tissues is complex, collagen II fibrils and aggrecan are the most abundant assemblies in the articular cartilage (AC) and nucleus pulposus (NP) of the intervertebral disc (IVD). Whilst structural heterogeneity of intact (three globular domain) aggrecan is well characterised, the extent of aggr...

High performance liquid chromatography (HPLC) equipped with photodiode array (PDA) detection from 190-800 nm spectral range has been a method in great demand in analytical chemistry of natural products that offers three-dimensional data set. This data set presents simultaneously the retention time of identified compounds over the spectral range of...