Mark Christian Research Group
The Christian Molecular Metabolism Lab at Nottingham Trent University
Our research focuses on understanding the molecular events that control cellular metabolism. We are characterising cells of the anatomically distinct white and brown adipose tissue depots and defining the action of hormones and dietary stimuli on adipocyte biology. Brown adipose tissue is an important target for combatting metabolic dysfunction as it serves to dissipate energy as heat. Our aim is to determine the actions of key factors that control the fundamental processes essential for the unique functions of brown adipocytes.
Recent Press Coverage
Brown Adipose Tissue
Energy homeostasis is crucial since excess fat storage leads to obesity and negatively impacts the body’s metabolic health with associated predisposition to diseases including diabetes and cancer.
There are two distinct types of adipose tissue:
1) White Adipose Tissue (WAT), when in excess, is considered to negatively impact on health due to its role in triglyceride storage and associated obesity.
2) Brown Adipose Tissue (BAT), in contrast, is considered to be favourable to health. Exposure to the cold rapidly activates signalling pathways in BAT which modulate gene expression and promote the capacity for thermogenesis and consumption of fat stores.
Remarkably, WAT depots can also respond to a long term cold stimulus by specific genetic and morphological changes that result in a more BAT-like appearance. We are investigating the factors and signalling pathways that control the function of brown adipocytes. These include pharmacological and natural plant-derived compounds.
Lipid Droplets
The study of factors that regulate lipid storage in different tissues is essential for understanding and controlling metabolic disorders.
Cellular lipid storage is determined by a group of proteins that coat lipid droplets and facilitate storage or utilisation by regulation of metabolic processes.
The brown fat protein CIDEA has important roles in lipid droplet formation and function. We have defined the molecular mechanism of CIDEA-dependent lipid droplet enlargement through binding of phosphatidic acid.
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Our work has identified a key role for CIDEA and lipid droplet dynamics in embryonic stem cells.
By studying the function and regulation of CIDEA, we are determining the impact of this protein on lipid storage in different cells and tissues, the importance of controlling the expression of metabolic regulatory systems in response to environmental stimuli, and the impact of cell-specific gene expression on cellular bioenergetics.
Gene Expression and Epigenetics
Our research is investigating the expression of both mRNA and microRNA by brown and white adipocytes.
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We are determining the role of specific genes and microRNA by genetic knockout and application of CRISPR/Cas9 gene editing technology.
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We are investigating the role of microRNAs in adipocytes and a mouse embryonic stem cell model of adipocyte differentiation.​
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Cellular Bioenergetics
We are using Seahorse Real-Time Cell Metabolic Analysis and Oroboros Instruments to characterise the effects of genetic manipulations and pharmacological treatments on oxygen consumption, energy substrate usage, and mitochondrial function.
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This technology is being applied to a range of cell types and isolated mitochondria. We are monitoring changes in energy substrate usage by a range of cell types including 3D organoid cultures.
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Projects include analyis of the effects of plant-derived compounds on adipocyte metabolism.
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RESEARCH
Primary Areas of Interest
Prof Christian was a lecturer at Imperial College London before being appointed as an Associate Professor at the University of Warwick. With funding from the BBSRC and European Union FP7 he has given new understanding to the key differences between brown and white adipose tissue as well as the mechanisms of lipid droplet enlargement. As a Post Doc researcher at Imperial College London his work in reproductive biology determined key steroid hormone-controlled molecular events that prepare the endometrium for implantation. He continued his research on steroid hormone action at the level of co-modulator interaction and determined actions of the co-repressor RIP140 in adipose tissue metabolism. He was appointed as a lecturer at Imperial College London and developed his research programme on brown adipocyte biology and the action of genes enriched in this tissue including the lipid-droplet-associated protein CIDEA. Following his appointment at the University of Warwick he investigated the role of G protein coupled receptors in brown adipocyte biology and expanded the study of CIDEA action to stem cell biology and continues these studies at Nottingham Trent University.
Prof Mark Christian
Professor of Metabolic Health
School of Science and Technology, NHB 163, Nottingham Trent University, Clifton, Nottingham, NG11 8NS
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