Grants

Developments in mass spectrometry (MS) based proteomics in recent years now allow for routine, large-scale analysis of post-translational modifications (PTM), such as phosphorylation. However, the PTM proline cis-trans-isomerisation lacks approaches for global, cellular identification and quantification, even though it plays important roles in physiological and disease context. In this research proposal, I will develop a novel multi-layered MS-based pipeline to study proline cis-trans-isomerisation. I will then apply my new pipeline to identify and functionally characterize peptidyl-prolyl isomerase substrate networks in physiological and disease model systems. By providing this workflow, I will enable the scientific community to gain novel insights into this so far elusive PTM and at the same time pave my own career path towards becoming an independent scientist in Denmark with a research niche in MS-based proteomics of cellular signalling.

Early arithmetic ability and strategy use correlates with general achievement in mathematics in later grades. This project will enhance the understanding of early strategy use in relation to 1) later mathematical achievement, 2) development of adaptivity and flexibility, and 3) gender differences in patterns of development. The project consists of state-of-the-art quantitative analyses of existing longitudinal (grades 1-6) data on 63 Danish students’ arithmetic strategy use and mathematical achievement combined with additional information on reading ability, motivation in mathematics and socio-economic background. A meta-analysis will clarify the extent to which existing research literature addresses and quantifies gender differences in strategy use, and how strong and consistent they are across age, school systems and problem types. The project’s results will have implications for research as well as practitioners in teacher education and primary school.

For this research project I propose to research the still growing group of artists in East Asia who are transforming themselves into permacultural and natural farmers, in battles for cultural and ecological belonging. Specifically I will explore why and how art-farms have been gaining impetus in Hong Kong, Japan, and Taiwan as a significant contemporary eco-artistic and political form, at places positioned concretely and figuratively in the border-zones of global imperial histories and current Sino-imperial expansion within the region. How does such practices amount to forms of socially engaged eco-art? And how do we de-centre Euro-American assumption about social art to understand the situated stakes and reasons for this particular form of art-farming. Theoretically, and methodologically I will explore this as an interdisciplinary endeavour, drawing on East Asian art theory of social art practices as well as anthropological methods of field-research and more-than-human ethnography.

The project examines the cosmologies of the experimental scientists A. Humboldt (Kosmos), H. C. Ørsted (Aanden i naturen), and G. Fechner (Zend-Avesta). By placing these cosmologies in their philosophical and scientific context, the project aims at a historic and systematic account of the mutual influence between speculative philosophy, arts, and the natural sciences. Specifically, it is the ambition of the project to answer the following three questions: 1) How do these cosmologies position themselves in the surrounding scientific, artistic, and philosophical milieu? 2) What are the intentions; how do they relate to one another; and against which ideas do they react? 3) What are the main concepts, methods, arguments, and notions of science; and especially, what concepts of system, nature, and human being are developed in the three cosmologies? The expected outcome of the project is a nuanced understanding of this metaphysical tendency as a whole and its cultural importance.

Parkinson’s disease (PD) and Multiple System Atrophy (MSA) are both progressive neurodegenerative movement disorders characterized by accumulation of the protein alpha-synuclein (α-syn) in brain cells facilitating cell death. We hypothesize that dysfunctional immunological responses against specifically against α-syn are part of the disease pathogenesis. Thus, our aims are 1) to explore the α-syn specific antibody repertoires from healthy individuals in comparison with MSA and PD patients using epitope peptide microarray screening methods, in order to identify disease-specific immune signatures, 2) to identify the B cell receptor (BCR) repertoire memory B cells recognizing a-syn, 3) to integrate information from the epitope microarray analyses and the BCR sequences in order to produce novel anti-α-syn antibodies, and 4) to test the antibodies ability to recognize pathology on human PD and MSA brain tissue including neutralization properties in in vitro seeding assays.

The proposed project seeks to significantly increase the survival of patients with glioblastoma multiforme (GBM), the most common type of malignant brain tumor in adults.Despite much effort only 3 new treatments have been approved for GBM since 2005. The lack of progress in bringing GBM therapeutics into the clinic relates to a set of general challenges associated with brain tumors, including entering the brain, lack of targets, and a hostile tumor microenvironment. Immunotherapy with T cells genetically modified to express a chimeric antigen receptor (CAR) represents a promising alternative to current treatment options. With this approach the T cell effector functions can be redirected against the patients tumor cells. In the proposed project we aim to increase the therapeutic potential of CAR T cells against GBM by increasing both functionality and persistence utilizing novel production platforms and CAR designs to augment and endogenous immune response.

Aims: The proposed project will investigate if somatostatin (SST) receptor antagonism in the gut or brain improves blood glucose control. Background: Type 2 diabetes (T2D) is the result of regulatory failures in the brain and gut. GIP and GLP-1 are peptides released from the gut after food intake that stimulate insulin secretion to lower blood glucose. The release of GIP and GLP-1 is inhibited by SST. Most of SST is secreted from the gut however SST secreting neurons is also present in the brain in areas involved in food intake and glucose control. By state-of-the-art methods this project will elucidate if specific blocking of SST can affect food intake and increase incretin secretion. Methods: The project will be carried out in cell lines and mice which will include in vivo (glucose tolerance tests and injections in the brain) and ex vivo (isolated perfused small intestine) models. Outcome: Elucidate if targeting the SST system can be a potential therapeutic drug target to treat T2D.

The aim of this DFF Postdoc Fellowship is to reliably predict brain dynamics in depression using big neuroimaging datasets and state-of-the-art predictive modeling techniques. The datasets that we will use will be obtained from sharing of data across 13 neuroimaging centers worldwide. The importance of data sharing has increasingly been acknowledged by the neuroimaging community, as a solution to leverage optimal and maximally powered research, while simultaneously ensuring the rigor and reproducibility of the work. In collaboration with Prof. Poldrack, director of the Center for Reproducible Neuroscience at Stanford University, I propose to probe an important and pertinent question that so far has suffered from replication issues, namely whether serotonin transporter binding is abnormal in patients with major depressive disorder. The proposed project will highlight the major benefits of sharing data and allow for better understanding of the human brain in major depression.

Several studies have reported links between infectious diseases and cardiovascular conditions, but only few and small-scale clinical studies have investigated the relationship between malaria and cardiovascular health. The Malaria Heart Disease Study is a prospective longitudinal cohort study of a random sample of 900 patients from two neighboring cities in Brazil: Cruzeiro do Sul (malaria endemic zone) and Rio Branco (no malaria). The overall hypothesis is that patients who have (i) previously suffered from a malaria infection or (ii) patients with ongoing severe malaria will benefit from having an echocardiogram and blood tests performed as a screening tool to diagnose early cardiac impairment and prevent future cardiovascular disease. Objectives: Descriptive: To determine the prevalence of overt and asymptomatic cardiac dysfunction in malaria patients by the use of echocardiography and biomarkers. Prognostic: Obtain follow-up at 1- and 2- years after study inclusion.

The excellent performance of atomic clocks allows for fractional measurement uncertainties at the 10^-18 level in frequency. In recent years, however, the community has started looking to quantum enhanced systems as classical approaches are limiting the performance of these clocks. An appealing solution is to use light directly emitted from the atomic clock transitions through superradiant emission. The OverCLOCK project tackles the challenge of developing the first continuous superradiant laser using narrow optical transitions. Such a continuous superradiant laser is dependent on ultra-cold atoms flowing continuously through an optical cavity. The low atomic temperature allows excellent control of the atoms needed for high-accuracy quantum metrology and sensing. In addition the project aims to realize a a second laser using the same stream of cold atoms allowing, e.g., phase-coherence measurements and experiments with many-body entanglement.