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, and be part of an international scientific collaboration at the Maersk Tower www.maersktower.ku.dk.
Call for Applications 2019 - now closed
Many biological processes are characterized by daily variations that are controlled by the circadian clock. The central clock, located in the hypothalamic suprachiasmatic nucleus and entrained by light as an external zeitgeber (time-giver), contributes to synchronize peripheral clocks in nearly all cells of the body. Physical exercise is beneficial for skeletal muscle metabolism and systemic energy homeostasis and alters the expression of target genes involved in glucose metabolism, lipid metabolism and mitochondrial biogenesis.
Overall, exercise is widely recognized as a beneficial therapeutic strategy for human health through the remodeling of specific metabolic signaling pathways. Nevertheless, the most effective time of day to achieve beneficial effects on health remains unknown. This project is designed to test the hypothesis that exercise acts as a zeitgeber for molecular clocks in peripheral tissues and controls the expression of metabolic genes involved in substrate metabolism. We have identified specific exercise-responsive transcription factors that orchestrate metabolism in skeletal muscle in a time-of-day-dependent manner. This postdoctoral fellowship will be focused on determining molecular mechanisms controlling time-of-day-dependent reprogramming of circadian metabolic pathways.
The project will be performed in collaboration with Prof Juleen R. Zierath and Assoc Prof Jonas Thue Treebak. They perform systematic and integrated studies of in vivo physiology, cellular biology, functional genomics in genetically modified organisms, and targeted exercise therapy. They possess in-house technical expertise in animal handling and state-of-the-art technologies within cellular biology, molecular biology, and biochemistry required for completion of this project. This teamwork and collective know-how between the two supervisors will ensure feasibility.
Call for Applications 2019 – now closed. Next call will be in 2020 with new projects to choose from.
The Inuit in Greenland are an indigenous population with extremely good information about the genetic selection, social transition and the disease pattern (including a high prevalence of obesity and diabetes). Inuit is ideal to study the consequences of recent life style transition on the changing disease pattern.
The power of performing studies in the small, historically isolated Greenlandic population has been demonstrated by our previous work including Diabetologia 2018, 61(9):2005-2015, Nat Genet. 2018, 50(2):172-174, PLoS Genet 2016, 12, 6:e1006119, Science 2015, 349, 6254:1343-7, Am. J. Hum. Genet. 2015, 96, 1:54-69 and Nature 2014, 512, 7513:190-3.
The gut microbiota is likely to have an essential role in the increasing incidence of cardio-metabolic disorders in the Inuit population. Thus, insights into the global gut microbiome composition in Inuit and the complex interaction with the host genome to understand changes in Inuit disease risk profile are urgently needed, but currently lacking.
The idea is to perform integrated systems modeling of host-microbial microbiome data and human genetic and physiology data using a novel and global gut microbiome angle, with the perspective to improve our understanding of early stages of the development of obesity and type 2 diabetes. The future perspective is to understand the functional impact of the global gut microbiome on metabolism and to develop diagnostic, prevention and treatment programs for metabolic disorders. The specific objectives are to:
• Characterize the global gut microbiome (bacteria, virus and fungi) in Inuit.
• Study the interaction between the global Inuit gut microbiome and the Inuit genome by studies of the microbiome among carriers and non-carriers of known disease associated variants and perform a genome wide association study to identify novel host genetic microbiome associations.
Insulin resistance, dyslipidemia, and increased risk of type 2 diabetes are closely linked to obesity, but there is wide individual variability in the metabolic tolerance for carrying excess body fat. Among patients who are morbidly obese, up to 10% do not show any sign of metabolic dysfunction at all. In contrast, lipodystrophic patients who are unable to form subcutaneous adipose tissue, typically suffer from severe insulin resistance and other metabolic abnormalities. Overfeeding experiments have shown that given similar relative weight gain, individuals may be either protected from or predisposed to metabolic dysfunction. Furthermore, results from weight loss interventions for type 2 diabetes have shown that non-overweight individuals respond to substantial weight loss just as well as the obese in terms of conversion to normal glucose tolerance.
The present project will examine the hypothesis that the individual relationship between adiposity and metabolic dysfunction is genetically specified. Utilizing data from several large prospective cohorts and weight loss trials, you will examine the role of genetic differences in the longitudinal association trajectories between adiposity and metabolic abnormalities. You will also examine whether circulating markers linked to dysfunctional adipose tissue reflect these individual trajectories of adiposity and metabolic abnormalities. The expected results of the project will elucidate the causal mechanisms that couple obesity to metabolic dysfunction and may open avenues for identifying individuals with the highest risk of developing insulin resistance and type 2 diabetes if they gain weight.
Key metabolites function not only as energy sources and metabolic building blocks, they also act as extracellular signaling molecules, which are being recognized by and signal through specific, selective GPCRs in a manner very similar to hormones and neurotransmitters (Husted et al Cell Metabol. 2017). Classical concepts of metabolism as, for example how glucose stimulates insulin secretion are currently being rewritten to include important components of signaling metabolites being sensed by selective metabolite GPCRs often in an autocrine manner (Trauelsen et al Cell Metabol. 2018).
The present project deals with the Hydroxycarboxylic Acid Receptors (HCARs), which constitute a family of closely related metabolite GPCRs highly expressed and regulated in adipose tissue. Of these, HCAR1 (GPR81) is a sensor of lactate and HCAR2 (GPR109A) a sensor of b-hydroxybutyrate. The physiological role of HCAR receptors is poorly understood due to lack of useful pharmacological tools and genetic models. The present project is based on the notion that lactate and ketone bodies function as local extracellular signals of fuel availability and metabolic stress which in autocrine and paracrine manners are sensed by HCARs to reprogram adipocyte function. To probe this notion and to characterize the physiological role of HCAR1 and 2 in metabolism in general we have generated a number of unique, proprietary pharmacological tool compounds and novel genetic models, which will be used/characterized by the postdoc in close collaboration with other members of the Schwartz lab and the lab of Zach Gerhart-Hines as well as other labs at the Center.
The maintenance of mammalian energy homeostasis is highly dependent on coordinated and context-related locomotion. In times of food scarcity, internal metabolic cues are vital to ensure appropriate behavior for survival and thus locomotor activities must be prioritized between foraging for food, reproduction, and escape from predators. Despite locomotion and eating are so obviously intertwined and both essential behaviors for survival, the mechanisms by which specific motor programs are engaged to maintain energy homeostasis are not well understood. Two distinct MLR-related nuclei responsible for divergent but context-dependent locomotor behaviors were recently characterized by the Kiehn Lab (Co-PI) (Caggioano et al., 2018 Nature).
Here we offer a collaborative postdoctoral project that aims to evaluate how metabolic status adjusts locomotor programs towards context-dependent movements. Thus, a central objective of the project is to characterize physiological and molecular links between energy homeostasis and locomotion. To this end, the candidate will utilize a series of modern methods to study the neurobiology of movements and the neurobiology of energy homeostasis in rodents, including chemogenetics, optogenetics, in vivo electrophysiology and genetically driven trans-synaptic tracing. The postdoctoral fellow will benefit from the diverse and complementary expertise of the Clemmensen Lab (CBMR, UCPH) and the Kiehn Lab (Dept. Neuroscience, UCPH) as well as the outstanding research environment at the Faculty of Health and Medical Sciences, UCPH.
Transcription and translation of nuclear-encoded genes into functional products that control cellular metabolism is a fundamental dogma of biology. However, far less is known about how highly-active organelles, such as mitochondria, convey energetic status back to the nucleus to shape transcription and fine-tune metabolism.
This postdoctoral fellowship will focus on investigating this mitochondria-to-nucleus communication (a.k.a. mitonuclear control) in the context of adipose biology. The postdoc will take advantage of gain and loss-of-function cell and genetic mouse tools newly-developed by the Gerhart-Hines lab. In close partnership with Professor Chuna Choudhary from the Center for Protein Research at the University of Copenhagen, the postdoc will globally interrogate post-translational modification (PTM) signatures to identify the key mediators propagating mitochondrial signals to the nucleus. Transcriptomic analyses will be used to uncover the gene programs and candidate transcriptional regulators under mitonuclear control, in collaboration with Professor Susanne Mandrup from Southern Denmark University. The postdoc will employ a range of in vitro and in vivo methodology to evaluate how these mitonuclear regulators shape adipocyte metabolism and, consequently, systemic energy homeostasis. Additionally, the postdoc will have the opportunity to participate in the newly-established ADIPOSIGN consortium (www.sdu.dk/en/adiposign) of which Associate Professor Gerhart-Hines is a partner.
This project will begin by mapping potential connections between work on circadian biology conducted at CBMR, to research on time and environment from across the biological sciences, humanities and social sciences. This will identify key nodes for investigating the concept of ‘multicyclic being’, outlining pragmatic implications for scientific methodology in dialogue with Center scientists, and contributing to the pressing intellectual and political need to articulate the human as a complex, metabolizing ecosystem deeply imbricated with its environment (Alaimo 2016; Landecker 2013). The postdoc will also collaborate with a cross-media communications team and Center scientists, to develop a toolbox for communicating and depicting multicyclic, metabolic bodies, to be utilised across scientific communication environments and Medical Museion. A book proposal and/or exhibition proposal are expected to result from the 3-year project.
References: Alaimo, S. Minneapolis: University of Minnesota Press 2016, Gerhart-Hines, Z. & Lazar, M. Endocrine Reviews 2015, 36(3), 289-304, Landecker, H. & Panofsky, A. Annual Review of Sociology 2013, 39(1), 333-357 and Sassone-Corsi, P. & Christen, Y. Cham: Springer 2016.