The Centre of Excellence in Metabolic Integration (MetaScale) explores how metabolism is spatially organized across biological scales and how controlled exchange of metabolites links organelles, cells and organs into functionally integrated networks. We posit that plasticity of such metabolically linked networks sets a limit between healthy homeostatic responses and pathophysiology leading to disease.
MetaScale will study 1) how metabolically integrated networks develop, and 2) how they respond to external changes, such as nutrition. We also aim to identify 3) how metabolic integration is altered in disease and upon metabolic stress. Our ultimate goal is to target diseases via metabolic integration, either by reconstructing healthy networks or by finding metabolic by-passes.
Stem cells first generate and later maintain our tissues by producing cells for tissue function through differentiation, and new stem cells through self-renewal. Careful regulation of this process yields a balanced output of cells, but this balance is lost during aging and in many diseases. We aim to understand why.
Interestingly, cells in a complex tissue are metabolically distinct, reflecting their function. MetaScale groups found that in addition to certain cell type specific pathways, this specialization occurs also in pathways that are necessary to most cells, with metabolic division of labor between cell types effectively integrating their metabolism. In MetaScale we will probe how such metabolic specialization and integration emerges during development, and how metabolic compartmentalization in subcellular and cellular level influences stem cell function maintaining our tissues.
My group is interested in two outstanding questions in medicine and biology: why diseases manifest in a tissue-specific manner and why we developed to be multicellular organisms. We propose that these fundamental questions have partially similar solutions. Mitochondrial diseases are a perfect target to explore both questions, because they show exceptional clinical variability and because mitochondria are major regulatory hubs for homeostatic and stress-related metabolic pathways.
We posit that during development, cell-to-cell contacts form metabolic units that share house-keeping metabolic functions, allowing capacity also to functional diversification. We posit that such metabolic dependencies provided a huge advantage in the evolution of multicellular organisms, but also generate cell/tissue-type metabolic sensitivities for disease. In MetaScale, we explore such mechanisms, their responses to exogenous and endogenous stresses in the contexts of both organ-specific and systemic metabolism and in metabolic and degenerative diseases, aiming to find interventions and solutions for patients.
We are interested in understanding the mechanisms by which the key building blocks of biological membranes, lipids, are transported, stored and mobilized in mammalian cells. We study the principles of lipid trafficking and distribution in both physiological conditions and in pathological states related to lipid imbalance, such as human lipid storage diseases and lipodystrophies. To this aim, we collaborate with physicists and chemists to develop and employ improved methods for analyzing lipids in cells and tissues.
In MetaScale, we will investigate the dynamic interplay between the major lipid and energy storage organelles, lipid droplets, with lipid metabolic subdomains of the endoplasmic reticulum, mitochondria and peroxisomes, under metabolic fluctuations. We will also study the coupling of lipid transport and metabolism between cell types, e.g. stem cells and differentiated cells, and differentiated cells in physiologically relevant contexts, using in vitro and in vivo systems.
The aim of our group is to understand how nutrient sensing controls animal physiology and pathophysiology. Our research spans from regulatory mechanisms that are mostly cell intrinsic to mechanisms involved in interorgan communication. Recently, we have focused on nutrient control of organ homeostasis, i.e. mechanisms that regulate intestinal size and cellular composition as well as turnover through the regulation of stem cell activity.
In MetaScale our research aims at understanding the metabolic integration between cells within a tissue that undergoes dynamic turnover. Our main model system will be the Drosophila midgut, which allows us to do carefully controlled genetic experiments and to use advanced analytical methods to manipulate and characterize the metabolic state of cells. We aim to understand how the collective control of organ metabolism and controlled exchange of metabolites between cells guide the fate and differentiation of stem cells to adjust tissue remodeling.
We are focused on exploring the genetic and environmental determinants of fetal and childhood-onset cardiovascular disease. Pediatric cardiovascular diseases often have a genetic basis. However, maternal factors - such as metabolic state and the various environmental exposures encountered during pregnancy - can modify these genetic determinants influencing fetal development and the risk for early-onset cardiovascular disease in offspring.
In MetaScale we will utilize patient samples and data from Finnish biobanks and nationwide health care registers to study the individual and combined effects of genetic and maternal metabolic risk factors on offspring health. Specific attention will be paid to maternal diabetes and obesity as risk factors for increased offspring morbidity. Our aim is to identify novel disease mechanisms and modifiable maternal risk factors to prevent disease and to improve the health of future generations.
We are interested in how metabolic specialisation enables stem cells and cancer cells to thrive in demanding tissue environments. In particular, we seek to understand how intestinal stem cells and cancer-initiating cells acquire and use nutrients during cancer initiation and progression, and how these processes help tumours sustain growth and evade treatment.
Within MetaScale, we will map the metabolic landscape of intestinal stem cells and cancer-initiating cells using high-resolution spatial metabolomic imaging to visualize metabolism at cellular and subcellular levels. We posit that altered nutrient transport is not merely a consequence of malignant transformation, but a fundamental driver of disease and metabolic plasticity. By combining our expertise in cancer biology, genetic engineering, and spatial metabolomics, spatial multi-omics and clinical samples, we investigate how altered nutrient transport rewires tumour metabolism and drives cancer initiation, progression, and malignancy.
We are interested in developing innovative disease models and therapeutic strategies to better understand and treat metabolic disorders. Our research combines the use of stem cell-derived pancreatic islets, CRISPR-based genome editing and single-cell and functional genomics to unravel how genome regulation and metabolism orchestrate pancreas development and drive disease.
Within MetaScale, we investigate how metabolic integration emerges and develops at both the cellular and systemic level. We study the molecular nodes that coordinate the metabolic activities of individual cells and determine their function, plasticity and vulnerabilities. By mapping the intricate connections governing metabolic integration, we aim to improve the potency, safety and scalability of cell replacement and gene editing therapies for diabetes and other metabolic diseases.