CBMR International Postdoctoral Program
Applications closed on April 19, 2021
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 2021
Click the accordions below to read more about the 10 different projects on offer through the CBMR International Postdoc Program, and to apply.
The application period for 2020 will remain open between February 12 and April 19, 2021.
The concept of diagnosis plays multiple roles in medical practice and biomedical knowledge. It helps make sense of patient bodies, direct treatment, and enables researchers to focus their work through categorized body material. While humanities research has often focused on psychiatric diagnosis, diagnosis in somatic medicine holds great promise as a route to understanding medical knowledge between practice and science and to map connections between research, clinical medicine and patients.
Between Knowing and Doing will investigate how clinical diagnoses enter and are used in research, how they are transformed in different systems of research, and how differentiated diagnoses return to the clinic and patients. The work at the Center offers an opportunity to follow diagnostic categories in practice and across biomedical research and clinical medicine. The project will take its starting point working with the flagship project SEGMENT at the Center, which works with categorizing diabetes on several platforms, and then connecting findings to understandings of the concept of diagnosis from across the biological sciences, humanities and social sciences.
Drawing on a practice-embedded philosophically informed approach, the project aims to bring us closer to understanding how biomedical knowledge and disease categories are co-produced in the cases of obesity and diabetes. Methodologically the project might draw on concepts such as epistemic flexibility, ‘epistemic iterations’ as well as historical categories underlying current usage.
As part of the project an array of events and other forms of engagement will also take place at the Medical Museion involving patients, practitioners and the broader public.
Pre-conceptional exposure to environmental factors like diet, physical activity and endocrine disruptors can impact the health of the next generation. We and others have identified that epigenetic information carried in gametes is amenable to external influences, but the mechanism by which environmental factors establish specific epigenetic changes in gametes remains totally unknown.
In this project, we aim to determine how environmentally-influenced epigenetic information is transferred to spermatozoa. We hypothesize that under environmental stress, blood extracellular vesicles originating from somatic tissues deliver small RNA (sRNA) molecules to spermatozoa, thereby acting as carriers of epigenetic inheritance.
Mice models and investigations in human subjects will be used to map sRNA expression in blood extracellular vesicles and in sperm. The effect of specific sRNA-containing blood extracellular vesicles on offspring phenotype will be tested by injecting synthetic extracellular vesicles containing tagged candidate sRNA molecules and specific surface markers into the tail vein of male mice before mating. We will study the metabolic and behavioural phenotype of the next generation offspring at various ages.
These experiments will provide important insights into the role of the blood-borne sRNA-containing extracellular vesicles in paternal epigenetic inheritance.
Metabolic health and disease is deeply embedded in culture – what, when, and how we eat; how we move and exercise; our patterns of work and rest; all are in part culturally structured. Enabling a richer cultural understanding of the complexity of metabolic health and disease is thus one of the stated aims of the Center’s mission statement. This postdoc project contributes to this aim by focusing specifically on how aspects of metabolic activity have been taken up in artistic practice, both historically and in contemporary art.
The project will create novel readings of artworks by paying sustained attention to the metabolic qualities of relevant themes in the history of art – food, fat and feces. All three themes have long histories within art, and as such provide a rich source of empirical objects of study, which are resonant with a metabolic perspective.
The postdoc will be part of a larger undertaking by the Metabolic Science in Culture Program to develop a ‘metabolic humanities’, using metabolism both as topic and as inspiration for theoretical and methodological innovation. Around the metabolic processes of an individual body stretches a vast material-semiotic system, highlighting how bodies, substances, and environments mingle and draw attention to each other: interlocking cycles involving waste, food, bodies, environments, consumption, absorption, transformation. The project will follow this interweaving of the material and the semiotic through the history of art and artistic practices, showing how metabolisms appear both literally and in an expanded sense, in order to develop art and cultural theory around a vital and lively topic.
The science of energy homeostasis suggests that biological processes have evolved to ensure weight stability by actively matching energy intake to energy expenditure. Bodyweight thus appears to be regulated around a somewhat predetermined ‘set point zone’ that is largely resistant to conscious attempts to substantially change weight in either direction. In both lean and obese subjects, keeping weight below the biologically defended level by caloric restriction induces a series of potent counter-regulatory homeostatic responses that favor weight regain. Similarly, controlled experimental overfeeding, i.e. feeding volunteers with energy beyond their energetic needs, elicits a powerful homeostatic response that counters the positive energy balance.
The primary objective of this postdoc project is to identify and characterize novel signaling molecules (metabolites, peptides and proteins) that are secreted into circulation in response to experimental overfeeding in mice. Subsequently, candidate secreted factors will be evaluated in vivo for causal effects on appetite and body weight in mice.
Your tasks will involve employing an intragastric mouse model of overfeeding to study physiological and molecular defense mechanisms against excessive weight gain. There will be ample opportunity to contribute to the creative part of the project. This is a highly collaborative project and you will be interacting with numerous groups at the Center including the Groups of Schéele, Deshmukh and Gerhart-Hines. On a daily basis, you will work closely with several members of the Clemmensen Group, as this project synergizes with an overarching lab research objective of identifying novel and potent satiety signals that can be pharmacologically modified for the treatment of human obesity.
Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is a consequence of defects in intracellular signaling leading to failure in insulin-mediated effects on glucose and lipid metabolism. Insulin signaling diverges into multiple branches affecting every organelle of the cell, and for a subset of proteins, this involves translocation from one compartment to another (e.g. FOXO family proteins).
This illustrates that the insulin signaling is more complex and dynamic. Identifying these dynamics in skeletal muscle will reveal novel insight into insulin signalling and how muscle organelles respond in health and disease. The overarching aim of this research project is to identify and understand subcellular organelle level protein dynamics of insulin stimulated skeletal muscle. We hypothesize that that insulin regulates skeletal muscle metabolism through compartmentalization of proteins and phosphoproteins. The project involves application of mass spectrometry-based proteomics to map insulin-induced changes in organellar proteome and phosphoproteome in skeletal muscle from control and diet-induced insulin resistant mice.
We are seeking a highly motivated researcher with the strong expertise in proteomics bioinformatics. He/she will combine a range of models (cell, rodent and human), and functional metabolic analyses with cutting edge proteomics technology. For the relevant literature, please refer to these articles PMIDs: 16615899, 30352176, and 27278775.
The liver-derived hormone FGF21 seems to regulate preference for sweet foods with increased circulating FGF21 leading to a suppressed intake of sugars and artificial sweeteners. However, the knowledge regarding the effects of FGF21 on preference for sweet foods is derived mainly from animal data.
In the present study, we will establish, for the first time in humans, the effect of intravenously administered native FGF21 on 1) sweet taste preferences and food intake in a free-choice snacking buffet 2) the hedonic evaluation of sweet-tasting stimuli (i.e. consummatory behavior) 3) the motivational drive for sweet food stimuli (i.e. appetite behavior). Furthermore, sweet taste preferences, the hedonic evaluation of sweet-tasting stimuli, and the motivational drive for sweet food stimuli will also be assessed in a group of FGF21 receptor-deficient patients carrying FGFR1 loss-of-function variants. The successful candidate will be responsible for writing the protocol and other trial-related documents, execution of the study, data analysis, writing of manuscripts and presentation of results.
We believe that insights into the physiological mechanisms behind the regulation of the intake of sucrose-rich, sweet-tasting foods in humans could provide new opportunities to improve dietary quality and thereby add valuable treatment opportunities for patients suffering from lifestyle diseases caused by excessive sugar consumption.
This project is a part of an overall strategy of exploring the genetic and physiological background of dietary preferences and the relationship with metabolic diseases.
With the project ‘Genetic studies of extreme obesity in consanguineous Pakistani families’, it is our ambition to perform whole genome sequencing (WGS) in 130 Pakistani families with one or more children with extreme obesity, and to identify and characterize novel obesity genes. This will generate new insights into the function of novel obesity genes and it will facilitate studies of obesity in other populations, with the perspective to improve our understanding of early stages of the development of obesity.
The study will include 1) whole genome sequencing, 2) analysis of protein stability, 3) mapping obesity genes to cell types and 4) analysis of selected loci using recessive models in other study populations.
This project will enable us to identify novel genetic variations associated with early onset obesity. We will elucidate the impact of the disease associated variants on the molecular level combining biophysical modelling of protein folding and stability with advanced sequence analyses to interpret variant effects. Furthermore, in-house initiatives to characterize open chromatin and cell type specific gene regulation will allow us to map the effect of the variants to the cellular and tissue level. Finally, we will examine whether the gene/genes associated with childhood obesity in Pakistani families might be associated with obesity/BMI in other non-European populations, in Danish children with early onset obesity and in large populations based studies (i.e. UK biobank) applying recessive analytical models. The results will be used to propose and develop new approaches to diagnose, prevent and treat early onset obesity.
Cellular adaption to nutrient and metabolic stresses such as starvation and exercise are critical for the maintenance of organismal homeostasis. Cells have evolved tightly controlled “intra-cellular signaling systems” capable of sensing, transducing, and interpreting information such that the regulatory machinery can enact a coordinated and timely physiological response. AMP-activated protein kinase (AMPK) is an evolutionarily conserved regulator of energy homeostasis and a promising drug target for treatment of metabolic disorders.
We previously identified that a tumour suppressor protein kinase, LKB1, is an upstream regulator for AMPK and demonstrated that the LKB1-AMPK pathway plays a key role in mediating “insulin-independent (energy stress-dependent)” glucose uptake and energy homeostasis in skeletal muscle. We also identified key/novel mechanisms of action of small-molecule AMPK activators and provided molecular and physiological insights into their potential utility as tool compounds and future therapeutic applications.
The main goal of the project is to investigate the molecular and physiological roles for recently identified post-translational modifications (phosphorylation) within the regulatory subunit of AMPK. We will take both in vitro and in vivo approaches (e.g. using originally generated phospho-deficient knock-in mouse models) in collaboration with world-leading groups in the AMPK field. One of your key tasks is to perform detailed biochemical analysis of purified AMPK trimeric complex (wild-type and mutants) in the presence or absence of various agonists and also metabolic characterizations of the novel AMPK genetic mouse models.
Insulin resistance in peripheral tissues such as skeletal muscle and adipose tissue is characterized by an inability of the target tissue to appropriately modulate glucose disposal in response to a specific level of insulin. Insulin resistance precedes the development of type 2 diabetes (T2D) and is a consequence of ectopic lipid deposition in insulin responsive tissues.
NAD+ has emerged as an important cofactor linking energy status with adaptive cellular and organismal responses, and it serves as a substrate for multiple enzymes involved in the regulation of energy metabolism. Low cellular NAD+ levels could therefore prompt the development of many age-related disorders, including insulin resistance. Skeletal muscle act as an important sink for glucose clearance under insulin-stimulated conditions, and insulin signaling to glucose disposal in skeletal muscle in the context of insulin resistance has been studied intensively over many years.
We have preliminary data from quantitative mass spectrometric analysis of skeletal muscle that shows key proteins in the insulin signaling cascade are ADP-ribosylated. Since ADP ribosylation (ADPr) is mediated by NAD+-consuming ADP-ribosyltransferases, this indicates a yet unrecognized interplay between insulin signaling and cellular NAD+ metabolism. Our hypothesis is that ADPr plays an essential role in regulating insulin sensitivity in skeletal muscle, and our over-arching aim is to determine the role of this posttranslational modification (PTM) for maintaining cellular glucose homeostasis and insulin action.
An essential component of an organism’s survival is the ability to sense energy availability and to adapt accordingly. As such, cells contain highly conserved sensing mechanisms that monitor energy and nutrient status. These energy sensors are tightly linked with endogenous circadian rhythms and thereby contribute to the plasticity of liver, adipose tissue and skeletal muscle to maintain metabolic homeostasis throughout the day. AMP-activated protein kinase (AMPK) is a crucial cellular energy and nutrient sensor, which integrates stimuli such as metabolites, growth factors, and energy status.
Results from our group suggest that AMPK may be required as an energetic sensing mechanism controlling circadian core clock gene expression and metabolism. The main objective of this post-doctoral project is to determine the mechanism by which energetic stressors converge on AMPK signaling and the circadian machinery and elucidate the potential role of AMPK in influencing metabolic communication between tissues. The post-doctoral fellow will adopt multi-disciplinary approaches, integrating cell-based systems and animal models to validate whether AMPK pathways are involved in the clock-controlled changes in systemic metabolism.
This project will also include usage of transcriptomic and metabolomics platforms, as well as bioinformatics tools, and the successful candidate will therefore receive necessary basic training within these fields.