GRANTS. After the review process was completed, it became clear that five researchers at Sahlgrenska Academy have been awarded the Bollan Scholarship 2023. These researchers are conducting projects in the field of medicine and health and will be able to utilize the infrastructures at Core Facilities.
The award ceremony for the Bollan Scholarship 2023 was held on October 12th. Present to present the award were Elisabet Carlsohn and Marie Hornfelt, Heads of Core Facilities, and representatives from the Lindén family.
“It’s very exciting to see that we receive many applications every year and that the applications maintain a high quality. This year’s scholarship recipients are all working on exciting projects,” says Marie Hornfelt.
The expertise of four Core Facilities infrastructures will be utilized in the five approved projects. These include Proteomics, Mammalian Protein Expression, the Centre for Cellular Imaging, and the Bioinformatics and Data Centre.
“Connecting young promising researchers with outstanding projects to our research infrastructure is an important step for the collective development of the faculty. We view this type of collaboration very positively and are grateful for the bequest that enables us to carry out this valuable work”, says Elisabet Carlsohn.
The unit managers at Core Facilities first assess each application based on feasibility. Following that, the applications are evaluated and ranked by reviewers appointed by the Council for Core Facilities, representing various departments within the Sahlgrenska Academy, as well as representatives from Chalmers and the Västra Götaland Region.
The approved projects
Elisabeth Nyström
60 000 SEK to use at Core Facilities Mammalian Protein Expression
Project title: Identification of protease regulatory elements in CLCA1
Project summary: Increased expression of the protein calcium activated chloride channel regulator 1 (CLCA1) is highly associated with Th2-driven asthma and chronic obstructive pulmonary disease (COPD) but the outcome and relevance of this association is still unknown. However, the normal expression of CLCA1 is restricted to the intestinal mucus barrier, where we have shown that CLCA1 acts as a metalloprotease involved in structural re-arrangement of the mucus by cleaving the main structural component mucin-2. Preliminary data indicate that the proteolytic activity of CLCA1 is tightly regulated but the details regarding this regulation remain elusive. A common pathway of protease activation is proteolytic cleavage of the protease. Discovery of cleaved versions of CLCA1 in mucus, both by Western blot and by specialized mass-spectrometry based methods to detect neo-N-termini, indicate that this might be true also for CLCA1. We thus aim to investigate the hypothesis that CLCA1 proteolytic activity is regulated by post-translational cleavages. This which will be achieved by characterizing the proteolytic activity, biochemical properties and molecular structure of truncated versions of CLCA1 expressed and purified from mammalian cell lines by the Mammalian Protein Expression core facility.
Kristina Johansson
60 000 SEK to use at Bioinformatics and Data Centre vid Core Facilities.
Project title: Genetic reprogramming of goblet cell function in asthma
Project summary: Mucus overproduction limits the airflow in asthma. Persistence of mucus plugs suggests a functional reprogramming of mucus-producing goblet cells in asthma, although, a molecular definition of pathological goblet cell responses in the lung is still lacking. I have previously identified a microRNA that functions as a critical regulator of goblet cell metaplasia and mucus production in the airway. But several questions regarding the role of microRNAs in regulation of airway mucus remain. To identify mechanisms that link specific microRNAs to goblet cell dysfunction, I will use an experimental mouse model of asthma and perform total RNA sequencing of the airway epithelium containing goblet cells. With BDC’s expertise and infrastructure we will map microRNA:mRNA networks that define goblet cells in airway pathology.
Debora Dreher Nabinger
60 000 SEK to use at Centre for Cellular Imaging
Project title: Autism, oxytocin, and social interactions: Identification of neural mechanisms and drug targets
Project summary: Autism spectrum disorder (ASD) is characterized by deficits in social processes. Although severely affecting 1% of the population worldwide, no pharmacological treatment is available. Oxytocin has been proposed to impact and facilitate social processes, and interventions increasing endogenous oxytocin seem to be an attractive alternative to diminish social deficiencies in ASD. With the overall goal of developing treatment strategies for social deficits, this project aims to identify drugs enhancing oxytocin’s expression, and to decipher neural circuitry involved in oxytocin’s actions on social interactions. To identify drugs that stimulates oxytocin neurons, transgenic zebrafish larvae expressing eGFP in oxytocin neurons (oxtl:egfp) will be treated with a large number of drugs during early development. The number and size of eGFP-positive neurons as well as the intensity of the eGFP signal, here used as a proxy for oxytocin mRNA transcription, will be investigated in live fish before and after subchronic drug treatment. We use the state-of-the-art imaging technology using the Cell Discoverer 7 allowing drug screening in a 96-well format using regular as well as confocal microscopy. As a next step, we will explore the neuronal circuitry implicated downstream of the oxytocin enhancing drugs revealed in the first part of the project. Through a whole-mount immunohistochemistry approach using an antibody towards phosphorylated S6 (an endogenous sensor of neuronal activation) in drug-treated oxtl:egfp zebrafish, we aim to reveal to what extent a drug induce oxytocin expression and therefore sociability. For this second part of the project, as a super resolution method, the microscope LSM980 with Airyscan will be used for imaging, allowing us to scan the whole brain of zebrafish larvae looking to full brain activity. In conclusion, this project will hopefully identify substances that stimulate oxytocin release, and social abilities in patients.
Ermir Zulfaj
35 000 SEK to use at Proteomics
Project title: Proteomic Profiling in Takotsubo Syndrome and the Stress Response of the Heart in Comparison to Acute Myocardial Infarction
Project summary: Every moment of life is sustained by the relentless pumping of our hearts. It must do so, regardless of the stress present. Takotsubo syndrome (TS), also known as broken heart syndrome, is characterized by the sudden loss of heart function following acute emotional or physical stress—a condition that can affect anyone. The cause is unknown, it lacks disease-specific treatment, and its clinical presentation is indistinguishable from acute myocardial infarction (AMI), often leading to unnecessary invasive procedures. The significance of this loss of function in response to stress and why some people develop it, while others don’t, remains unknown. This project aims to understand the molecular pathways of TS and AMI using quantitative proteomic profiling analysis. The study design involves profiling the heart’s proteome in different states using in-vivo models of AMI and our recently developed world-leading model of TS in rats. This type of comparative study has never been done before, and we are currently in a unique position to undertake it. We hypothesize that the cardiac proteomic changes underlying the pathophysiology of TS differ from those in AMI and represent a promising avenue to identify (1) potential therapeutic targets, (2) diagnostic biomarkers, and (3) to enable proof-of-concept studies.
Charlène Perian
35 000 SEK to use at Proteomics
Project title: Collagenous peptides as biomarkers for adipose tissue dysfunction and increased risk for type-2 diabetes.
Project summary: Physiological subcutaneous adipose tissue (SAT) expansion protects the body from harmful lipid deposition in the visceral compartment, thus decreasing the risk for metabolic diseases. The expandability of SAT is dependent on enzymatic extracellular degradation of fibrillar collagen. The resultant collagenous peptides are removed via macrophage-mediated lysosomal degradation. This macrophage function is impaired in diet-induced obese/insulin resistant mice associated with accumulation of short collagenous peptides in SAT. Moreover, such peptides exert fibroinflammatory action in vitro suggesting that they contribute to adipose tissue dysfunction. We now aim to translate these findings to the clinic. Human SAT collagen fragments will be measured by a mass spectrometry-based method that we recently have established together with Dr Jonas Nilsson and Dr Carina Sihlbom at the Proteomics core facility. We hope these analyses will allow us to identify specific collagenous peptides as biomarkers of adipose tissue dysfunction.
BY: AMELIE KARLSSON
