CBMR International Postdoctoral Program
The CBMR International Postdoctoral Program supports competitive international recruitment of postdoctoral fellows to the Novo Nordisk Foundation Center of Basic Metabolic Research.
The postdoctoral research fellowships are aimed at early career researchers with a basic science background or clinicians who aspire to a career in academic medicine. We are particularly interested in candidates who are familiar with integrative research approaches within the broad area of basic metabolic research with an application towards human pathophysiology.
Each postdoctoral fellow will receive a competitive package including salary and running costs for three years.
Postdoc projects starting in 2022
Click the accordions below to read more about the 5 different projects on offer through the CBMR International Postdoc Program, and to apply.
The application period for 2022 will remain open between February 11 and April 11.
Brown thermogenic adipocytes have unparalleled energy-expending capacities with therapeutic potential to treat metabolic disease. Adipose thermogenesis is activated by exposure to environmental cold, which stimulates thermogenic catabolism of lipids and carbohydrates. This physiological response improves metabolic homeostasis and is strongly controlled by G protein-coupled receptors (GPCRs). This includes the canonical thermogenic effectors, the b-adrenergic receptors (bARs), as well as the secretin, glucagon, gastric inhibitory polypeptide, and adenosine receptors. Yet despite the profound ability of adipose thermogenesis to improve energy homeostasis and counteract metabolic disease, the prevalence of classical brown adipocytes in humans remains highly debated. However, subcutaneous white adipocytes are ubiquitously present in man and can be rendered thermogenically viable. Similar to classic brown adipocytes, activated subcutaneous adipocytes can significantly improve metabolic health. Therefore, understanding what signaling pathways promote the thermogenic competence of this adipocyte subtype poses immense therapeutic potential. Moreover, our knowledge of this process in humans is virtually nonexistent. To this end, in this CBMR international postdoctoral fellowship, we seek to investigate GPCR signaling in human adipose during thermogenic activation to improve our basic understanding of physiology and potentially uncover new therapeutic targets for obesity.
High body fat mass and low lean mass in proportion to body size are strong predictors of morbidity and mortality. At the population level, body fat and lean mass are closely correlated. Thus, persons with higher fat mass have on average higher lean mass as well. However, at the individual level, there is wide variability in the relative proportions of fat and lean mass. Genetic associations provide unique opportunities for identifying the causal mechanisms that underlie this variability. Intriguingly, we have discovered many genetic variants that contrast the strong positive correlation between fat and lean mass in the population – the variants are associated with higher fat mass but lower lean mass.
In the present project, we aim to identify the mechanisms that underlie the genetic associations with higher fat mass but lower lean mass. The studies will focus on investigating gene functions in the main constituent tissues of body composition: adipose tissue, skeletal muscle and bone. By integrating genetic association data with data on gene expression and gene regulatory annotations, we will assess the mechanisms that underlie the genetic associations with higher fat mass but lower lean mass. The analyses will guide gene perturbation studies in vitro and in vivo, to verify and further understand the mechanisms.
In 2019, we (Pedersen et al.) discovered a bacterial polypeptide hormone synthesized of four bacterial strains in the human gut microbiome. Subsequently cellular studies and studies in rodents show that the hormone enhances thermogenesis, and bone metabolism and lowers blood glucose and body weight. Furthermore, preliminary single-nucleus RNA-sequencing experiments show that the bacterial hormone impacts neuronal circuits. Based on these observations and additional preliminary data, we hypothesize that the bacterial hormone improves metabolic and cognitive health in part through alleviation of neuroinflammation in brain areas that are known to regulate energy homeostasis and cognitive function.
The overarching aim of our proposal is to systematically map brain cell populations and molecular signaling pathways through which the bacterial hormone exerts its beneficial effects on metabolic and cognitive health. First, we will map brain nuclei being activated following treatment with the bacterial hormone in mice using light sheet fluorescence microscopy and the immunolabelling-enabled imaging of solvent-cleared organs-technique (iDISCO) to quantify whole-brain cFos expression across 308 brain areas. Next, focusing on the most responsive brain areas, we will apply multimodal single-cell and in situ sequencing techniques to identify activated cell populations and characterize their cellular phenotypes. Finally, we will leverage transgenic mouse models and in vivo pharmacology to test specific hypotheses on genes and pathways modulating the beneficial effects of the bacterial hormone on metabolic and cognitive health. Throughout the project, data science and machine learning techniques will be used to generate specific hypothesis informing subsequent experiments and to optimize the data-to-insight process.
'Role of NAD+ biosynthesis pathways in satellite cell function and recovery from skeletal muscle injury'
The regenerative properties of skeletal muscle depend on the myogenic ability of resident muscle stem cells (satellite cells) to replace mature myofibers. Satellite cells are in a metabolically and mitotically quiescent state throughout adulthood, but undergo multiple rounds of proliferation and self-renewal in response to myofiber damage. With aging there is a loss of satellite cell quiescence, and satellite cells more readily enter a pre-senescent state impairing their function. Satellite cell regulation and senescence has been extensively studied, but the molecular nodal points for the age-related decline in skeletal muscle regenerative capacity and impairments in satellite cell function are unclear. Proper muscle function requires fine-tuned regulation of cellular NAD+ metabolism. NAD+ is an abundant pyridine nucleotide and it is a necessary cofactor for ATP generation to maintain cellular energy supply. In addition, NAD+ is a substrate for multiple enzymes involved in cellular metabolism. NAMPT maintains skeletal muscle NAD+ levels, and NAMPT in skeletal muscle is lower in older individuals, indicating an age-dependent reduction in NAD+ salvage capacity. NAD+ repletion improves satellite cell function and to accelerate muscle regeneration in aged mice. Thus, we hypothesize that NAMPT-mediated NAD+ biosynthesis plays an important role in satellite cell function and skeletal muscle regeneration, and the over-arching goal of this project is to determine the importance of NAD+ biosynthetic pathways in satellite cells for the ability of the skeletal muscle to recover from injury. Knowledge obtained in this project may form the basis for prevention strategies for age- or disease-related loss of muscle function.
Circadian rhythms are driven by an internal biological clock that is synchronized by Zeitgebers (time-keepers) that anticipate day/night cycles to optimize the physiology and behavior of organisms. The circadian program is regulated at both a central and peripheral level, and cell autonomous circadian rhythms are generated by a transcriptional auto-regulatory feedback loop. A basic paradigm of circadian regulation of metabolism is that oscillations of gene expression generate daily rhythms in cellular metabolism. While disrupted circadian rhythms alter metabolism, the extent to which these processes are impaired in humans with obesity or type 2 diabetes is unknown.
The main objectives of this post-doctoral project are to 1) determine the mechanisms and signals by which the core clock regulates mitochondrial rhythmicity, 2) investigate how the circadian transcriptional machinery is disrupted in type 2 diabetes, and 3) validate the role of candidate transcription factors and signaling pathways on circadian rhythmicity in transcription and mitochondrial respiration.
The post-doctoral fellow will adopt multi-disciplinary approaches, integrating cell-based systems and animal models to investigate the bidirectional relationship between the circadian clock and metabolism in type 2 diabetes. This project will include usage of mitochondrial respirometry, microscopy, and various “omics” approaches (e.g. proteomics, transcriptomic and metabolomics) as well as bioinformatics tools, and the successful candidate will therefore receive necessary basic training within these fields. Proteomics studies will be carried out in collaboration with the Deshmukh Group at CBMR.
Read more and apply