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Advancing diagnosis and therapy: Exploring the cancer microbiome

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Published on Tuesday, 23 March 2021

Six new interdisciplinary research projects have received multi-year funding in the context of the Audacity funding instrument of the University’s Institute for Advanced Studies.

The research project CAMEOS “Cancer Microbiome: Emergent Organisation and Stability across scales”, led by biologist Dr Elisabeth Letellier and physicist Prof. Anupam Sengupta from the Faculty of Science, Technology and Medicine aims to understand the largely unexplored cancer microbiome.

CAMEOS pioneers a new exciting line of cross-disciplinary research on the cancer microbiome that lies at an intersection of physics, biology and machine learning (ML). CAMEOS will explore the role of microbes – microorganisms which make up the microbiome – in shaping cancer characteristics and micro-environments, in relation to microbial species and their physiology.

Human microbiomes – the community of microorganisms associated with the human body – have been implicated as contributors to cancer genesis and development. Despite the recent breakthroughs in the realms of microbiomes and cancer research – two complex systems on their own – much remains unknown at their interface, the cancer microbiome. Though a growing body of fundamental and translational research indicates correlations between microbiome and cancer progression, the mechanistic underpinnings are grossly unexplored.

The cancer microbiome is especially important for cancer types which do not have a genetic cause, but which are caused by lifestyle factors. The cancer microbiome is a coupled active complex system in which certain properties support oncogenic (tending to cause tumours) attributes and progression. On the other hand, studies on how cancer cells impact an associated microbiome, are still in their infancy. “Little is known if and how emergent properties – which arise due to coupling between the two complex systems – regulate the dynamics of the cancer microbiome, thus leaving open a major gap in the efforts to predict cancer fate and progression. CAMEOS aims to innovatively harness this promising, yet unexplored functional parameter to advance the next generation of diagnostic and therapeutic tools,” says Prof. Anupam Sengupta.

Advancing knowledge about colorectal cancer

Focusing on colorectal cancer (CRC) as model system, CAMEOS will characterise the CRC and study how the associated microbiome influences the tumour micro-environment, using on-chip and organoid-based platforms. ML-based analytical approaches will capture the micro-scale changes and reveal how microbes regulate CRC and its micro-environmental (matrix) properties, ultimately impacting the organisation and metabolism of the microbes. Crucially, through time-series data, CAMEOS will generate unprecedented knowledge that will link CRC-matrix transformations with microbial distribution and physiology, revealing feedbacks that stimulate benign-to-malignant changes in cancer cells. “CRC is the best study model when it comes to the microbiome and cancer. Indeed, the gut is the organ of choice for this project as millions of bacteria reside within the gut. Therefore, it is widely believed that the microbiome has an important role in CRC even though cause and causality are not clearly defined yet,” says Dr Elisabeth Letellier.

Dr Elisabeth Letellier co-heads the Molecular Disease Mechanisms (MDM) Group at the Department of Life Sciences and Medicine at the University of Luxembourg. The MDM group has a strong focus on the analysis of mechanisms underlying tumour progression as well as the identification of biomarkers. Together with her team, she has developed patient-derived 3D tumour models, as well as different relevant in vivo CRC models, which allow to identify targets and develop therapeutic strategies.

Prof. Anupam Sengupta leads the Physics of Living Matter Group within the Department of Physics and Materials Science. The Physics of Living Matter is a cross-disciplinary team that focuses on microbial active matter, spanning research questions in ecology and environment, human health, biomaterials and biofluid dynamics.

CAMEOS is scheduled to start in September 2021.

More information about the Institute of Advanced Studies