Professor and principal investigator Nils Joakim Færgeman has since 2003 headed a research group at the Department of Biochemistry and Molecular Biology, University of Southern Denmark, which has applied multidimensional approaches including proteomics, transcriptomics, lipidomics, metabolomics and microscopy to investigate the regulation of lipid signaling and lipid metabolism. Nils Joakim Færgeman received his PhD in 1997 in molecular cell biology at Odense University, and spent two years as a postdoctoral fellow in Professor Concetta DiRusso and Professor Paul Blacks laboratory at Albany Medical College in Albany, NY, USA. Nils J. Færgeman returned to University of Southern Denmark in 2000 as an assistant professor, become associate professor in 2003 and was appointed full professor in 2012. He has for many years been renowned for his contributions to the field of lipid biology and metabolism and in particular lipid mediated signaling using genetics tools in yeast, C. elegans and mice. Nils J. Færgeman is involved in numerous scientific societies and member of the educational committee within Danish Diabetes Academy. He has supervised and mentored more than 25 Master, PhD students and Post docs, and in 2009 he was honored the best teacher at the Science Faculty at University of Southern Denmark.
Head of research: Professor Nils J. Færgeman
Academic staff Ditte Neess Pedersen
PhD student Eva Bang Harvald
PhD fellow Anne Sofie Braun Olsen
PhD fellow Hanne Engelsby
PhD student Vibeke Hedeholm Kongstad Kruse
PhD fellow Leena Karimi (co-supervisor)
PhD Fellow Kathrine Brændgaard Dall
Visiting PhD student:
Rikke Kruse Henriksen
Molecular, cellular and integrative physiology
The major theme of our research revolves around how metabolism and signalling are coordinated to meet the nutritional needs of cells and organism with emphasis on how lipids are synthesized, transported and metabolized and how they act as signalling molecules. We aim at understanding the relationship between lipid metabolism and lipid mediated signalling in the development of various diseases like obesity, diabetes, neurological disorders and cancers. Many of the signalling pathways and components that we focus on are evolutionarily conserved so much information can be obtained relevant to complex organisms by studying simple eukaryotes, like the yeast Saccharomyces cerevisiae the nematode C. elegans and mice. Hence, we use these model organisms and mammalian cells combined with molecular genetics and advanced analytical techniques to decipher how metabolism is regulated at the molecular level and how lipids can act as signalling molecules and their role in maintenance of cellular homeostasis.
Current research Projects
Regulation of sphingolipid metabolism and differentiation of human progenitor cells
The development of several metabolic and neurological diseases including diabetes, Parkinson’s disease, Alzheimer’s and epilepsy has been associated with impaired synthesis of complex lipids like ceramides and sphingolipids. Ceramides are at the central hub of sphingolipid metabolism and despite that ceramide synthases, which are involved in the synthesis of ceramides, have been characterized considerably, their in vivo role in mammals and how they are regulated remain elusive. We are interested in understanding how disturbances in ceramide and sphingolipid metabolism affects cellular differentiation and cell fate e.g. differentiation of human neural progenitor cells to neurons and glial cells. Moreover, we aim at understanding how ceramide synthases are regulated at the molecular level via post-translational modifications and by interactions with other proteins.
Regulation of autophagy and longevity
During the past decade autophagy has been recognized as a vital biological pathway that functions to promote health and longevity. Autophagy is a conserved lysosomal degradation pathway, in which a cell self-digests its components, which provides nutrients to maintain crucial cellular functions during fasting and rid the cell of excessive or damaged organelles, misfolded proteins, and invading microorganisms. Although recent work show a central role of TORC1 and other kinases in the regulation of autophagy, the role of posttranslational protein modifications underlying how autophagy is initiated and regulated still remain elusive. We have used SILAC-based quantitative phosphoproteomics to globally profile how MCF7 breast cancer cells respond to various inducers of autophagy and by bioinformatics analyses, we have identified phosphorylation profiles that predict the formation of autophagosomes. We are interested in further examining the role of these components and their modification in regulation of autophagy and longevity, and use both C. elegans and mammalian cell lines to address their specific functions.
Epidermal barrier function and integrative physiology
We have recently shown that functional loss of acyl-CoA binding protein (ACBP) impairs the epidermal barrier function in mice and leads to profound accumulation of lipids in the liver and hepatic suppression of the genes regulated by the Sterol Regulatory Element-Binding Proteins SREBP-1a/c and SREBP-2, which is due to an increased flux of fatty acid from the white adipose tissue to the liver. We hypothesize that disruption of the epidermal barrier function induce lipolysis in adipocytes, which results in increased flux of fatty acids to the liver and to extra-hepatic tissues, where they are incorporated into diacylglycerols, triacylglycerols and ceramides, which have detrimental effects on central cellular functions and may induce insulin resistance. We are therefore interested in characterizing the unanticipated role of the epidermal barrier function in whole body physiology.
Circadian rhythm and metabolism
Circadian clocks orchestrate daily physiology and metabolism but recent findings suggest that food-related signals modulate these rhythms. We are using large-scale integrative proteomics and lipidomics approaches to investigate protein and lipid levels in mice tissues as a function of the circadian rhythm. The temporal profiles show that a subset of proteins and specific lipid species display circadian oscillation as well as food-specific responses, which comprise specific metabolic networks including insulin-signaling and lipid metabolism. Further integration of tissue-specific datasets will enable us to delineate systemic behavior of circadian- or food-dependent regulation of lipids and proteins involved in lipid metabolism, and reveal novel regulatory circuitries, which regulate lipid metabolism.
Transcriptional regulation of phospholipid metabolism
Most of the structural genes required for biosynthesis of phospholipids in S. cerevisiae incl. INO1, PIS1, PSD1, PSD2, CHO1, CHO2 and OPI3 are coordinately expressed at the transcriptional level. This is accomplished by UASINO elements found in the promoter sequences of the respective genes. In the absence of the two metabolites inositol and choline, the transcriptional repressor Opi1 is sequestered in the ER-membrane by binding to PA and by interacting with Scs2. Upon addition of inositol and choline, PA is quickly consumed for the synthesis of PI, followed by translocation of Opi1 to the nucleus where it represses UASINO dependent expression indirectly by repressing the activities of the transcriptional activators Ino2 and Ino4. By mass spectrometry-based proteomics, we have profiled global changes in the yeast phosphoproteome in response to inositol supplementation and by subsequent bioinformatics and functional analyses, we are identifying novel signaling pathways and hub proteins, which are involved in the global cellular response to inositol supplementation.
Delayed Hepatic Adaptation to Weaning in ACBP-/- Mice is caused by Disruption of the Epidermal Barrier
Neess, D.; Bek, S.; Bloksgaard, M. M.; Marcher, A. B.; Færgeman, N. J.; Mandrup S., Cell Reports, 2013, 5(5), 1403-12
Reduced Ceramide Synthase 2 Activity Causes Progressive Myoclonic Epilepsy
Mosbech, M.; Olsen, A. S. B.; Neess, D.; Ben-David, O.; Klitten, L. L.; Larsen, J.; Sabers, A.; Vissing, Nielsen, J. E.; Hasholt, L.; Klein, A. D.; Tsoory, M.; Hjalgrim, H.; Tommerup, N.; Futerman, A. H.; Møller, R. S.; Færgeman, N. J., Ann Clin Transl Neurol, 2014, 1(2), 88-98
Glucose- and nitrogen sensing and regulatory mechanisms in Saccharomyces cerevisiae
Rødkær, S. V.; Færgeman, N. J., FEMS Yeast Research, 2014, 14 (5), 683-696
Quantitative proteomics identifies unanticipated regulators of nitrogen and glucose starvation
Rødkær, S. V.; Pultz, D.; Brusch, M.; Bennetzen, M. V.; Falkenby, L. G.; Andersen, J. S.; Færgeman, N. J., Mol. Biosyst., 2014, 10, 2176-2188
A full list of publications by professor Nils J. Færgeman can be found here.