The Speakers
Prof. Olivia Merkel
Ludwig Maximilian University of Munich, Germany
Webpage: https://www.cup.lmu.de/pb/aks/merkel/
Topic of the talk: Treatment of lung diseases via siRNA inhalation delivery
Abstract: New RNA formulations are imperative for clinical RNA delivery beyond the liver. The lung offers undruggable targets which could be treated with RNA therapeutics. However, approved siRNA formulations are not suited for pulmonary delivery due to instability in lung surfactant and during nebulization. This talk will focus on siRNA nano- and nano-in-micro-formulation for inhalation delivery to the lungs and subsequent treatment of a range of lung diseases as assessed in sophisticated in vitro, ex vivo and in vivo models.
Prof. Paola Luciani
University of Bern, Switzerland
Webpage: https://lucianiresearch.com
Topic of the talk: Targeting fibrosis in multiple organs via lipid-based drug delivery systems
Abstract: All organs undergo tissue repair through a complex multi-step mechanism involving the production of fibrotic tissue, resulting from a temporary increase in the deposition of components of the extracellular matrix (ECM). This natural and healthy process, a pivotal part of the wound healing response, may become aberrant when the injury is severe or repetitive, leading to an abnormal accumulation of ECM and critically compromising organ performance. Chronic fibrotic diseases affect the quality of life of patients and their families, and imposes burden and costs on society; nevertheless, only two antifibrotic drugs are approved to date, nintedanib and pirfenidone, both for idiopathic pulmonary fibrosis.
To address this unmet clinical need, our research group investigates the antifibrotic potential of bioderived and bioinspired drug delivery systems for systemic and local administration in various fibrotic pathologies: liver fibrosis, intestinal fibrosis and fibrosis of the endometrium. While we focused on formulating bioactive polyenylphosphatidylcholines for the treatment of liver fibrosis and on understanding the role of intercellular communication on imbalanced cellular homeostasis upon treatment, we repurposed pirfenidone for the local treatment of endometriosis and intestinal fibrosis using two different multicomposite drug delivery systems. Our approach aims at shifting perspective in the field of antifibrotic treatments and at proposing underexplored therapeutic avenues to tackle fibrosis in multiple organs.
Prof. Ola Söderberg
Uppsala University, Sweden
Webpage: https://www.researchgate.net/profile/Ola-Soederberg
Topic of the talk: Development of novel molecular biology tools for medical research
Abstract: Methods and technologies for cell analysis are a cornerstone in research and healthcare, facilitating researchers in answering questions about the origins and progression of disease, and helping clinicians to set a correct diagnosis. Over the last two decades my research has been mainly focused on the development of methods; such as in situ PLA, ProxHCR and MolBoolean; to provide the ability to monitor protein-protein interactions and post-translational modifications in fixed cells and tissues, which is essential for the studies and understanding of cellular signaling. These methods use DNA as a reporter molecule and are based on natural occurring enzymes. Our current research explores the possibility to go beyond the boundaries of what nature can provide, to design enzymes that cannot be made through evolution. We have recently engineered a DNA-polymerase that isn´t compatible with life, that provides unique opportunities for development of novel methods for medical research. I will present novel methods for analysis of signal transduction, analysis of DNA damages; and also possible new model systems for studies of cancer development.
Prof. Jens Carlsson
Uppsala University, Sweden
Webpage: https://www.carlssonlab.org
Topic of the talk: Antiviral drug discovery by virtual screening of ultra-large chemical libraries
Abstract: Antiviral drugs to treat coronavirus infections are urgently needed as a complement to vaccines and could save millions of lives in the inevitable future pandemics. During the COVID-19 pandemic, our interdisciplinary research team at Uppsala University have discovered potent inhibitors of the SARS-CoV-2 main protease, an essential enzyme for viral replication. The project was carried out in collaboration with platforms at the Science for Life Laboratory (SciLifeLab), which gave us access to state-of-the-art infrastructure for academic drug discovery. My research group explored two virtual screening strategies to find inhibitors of the main protease in ultra-large chemical libraries. Firstly, structure-based docking was used to screen a diverse library with 235 million virtual compounds against the active site. One hundred top-ranked compounds were tested in binding and enzymatic assays. Secondly, a fragment discovered by crystallographic screening was optimized guided by docking of millions of elaborated molecules and experimental testing of 93 compounds. Three inhibitors were identified in the first library screen, and five of the selected fragment elaborations showed inhibitory effects. Crystal structures of target-inhibitor complexes confirmed docking predictions and guided hit-to-lead optimization, resulting in a main protease inhibitor with nanomolar affinity, a promising pharmacokinetic profile, and broad-spectrum antiviral effect in infected cells. Strategies to accelerate drug discovery using virtual screening will be discussed.
Prof. My Hedhammar
KTH, Spiber Technologies, Sweden
Webpage: https://www.kth.se/profile/myh , https://spiber.se
Topic of the talk: FN-silk membrane as mimic of basement membrane in tissue barrier models
Abstract: The availability of relevant in vitro models of various tissue units would be highly valuable for our struggles to understand human biology and physiology to obtain better health solutions. In the native tissue, cells are distributed in various types of microenvironments, organized by a supporting extracellular matrix (ECM). Proteins in the ECM build up the frameworks of these different environments, e.g. interstitial matrix fibers in connective tissue and basement membranes in biological barriers. We have engineered a recombinant spider silk protein, FN-silk, that is functionalized with a cell adhesion motif from the ECM protein fibronectin (FN). FN-silk has the unique ability to self-assemble into a nanofibrillar membrane at the air-liquid interface. The FN-silk membrane mimics the basement membrane in several aspects, since it is ~1 um thin and composed of a mesh of nanofibrils where molecules, but not cells, can pass through. We are now using the FN-silk membrane to construct physiologically relevant tissue barrier models of, e.g. the blood-brain-barrier and the intestine.
Prof. Yvonne Perrie
University of Strathclyde, Scotland
Webpage: https://pureportal.strath.ac.uk/en/persons/yvonne-perrie
Topic of the talk: Formulation strategies for the delivery of mRNA vaccines
Abstract: The efficacy of messenger ribonucleic acid (mRNA) vaccines is now well demonstrated, leading to the use of mRNA-based COVID-19 vaccines delivered using lipid nanoparticles. Lipid nanoparticles (LNPs) are a key component of these vaccines as they protect the mRNA from degradation in the body and mediate delivery into the cytoplasm of cells. Generally, LNPs are comprised of various ratios of a neutral structural lipid, cholesterol, a PEG-lipid (to control particle size) and an ionisable lipid (which is cationic at low pH and thus binds the mRNA, and near-neutral charge at physiological pH). However, there is a wide range of choices to consider when designing an optimal mRNA-LNP formulation, and the impact of the lipid choice and combination selected is not well understood. Therefore, within our laboratory we are focused on investigating the role of LNP formulation on mRNA-LNP function and also ensure multi-scale processes and also the link between efficacy and route of administration.
Assoc.Prof. Daniel Espes
Uppsala University, Sweden
Webpage: https://www.scilifelab.se/fellows/daniel-espes/
Topic of the talk: Novel imaging techniques and drugs for targeting human pancreatic islets
Abstract: Type 1 diabetes is characterized by an immune-mediated progressive destruction of insulin-producing beta-cells within the pancreatic islets. At onset of disease, 60-70% of the beta-cell mass have already been lost. An adequate mass and function of beta-cells is crucial for maintaining normal glucose control, a fact that is painfully evident in type 1 diabetes. Within the human pancreas 1-2 million pancreatic islets is scattered throughout the organ. Since pancreatic islets have an average diameter of 150 µm current clinically applicable imaging techniques lack the resolution to detect single pancreatic islets. Therefore, most of our current knowledge on alterations of beta-cell mass and immune infiltration is based on autopsy studies. Positron Emission Tomography (PET) imaging cannot detect individual islets due to the inherent resolution of the PET scanner but could, given that an optimal tracer for beta-cells is identified, provide an accurate and quantitative integrated signal of the entire beta-cell mass within the pancreas. We are currently investigating how novel PET-tracers could increase our understanding of how beta-cell mass is altered in type 1 diabetes and also if it could be applied to image immune infiltration of the pancreas in early stages, and perhaps even pre-symptomatic stages, of the disease. In addition, we are investigating how different drug therapies could serve as regenerative agents, i.e. induce proliferation of remaining beta-cells, and if cellular therapies such as mesenchymal stem cells could be used to halt the progression of beta-cell loss in type 1 diabetes.
Assist.Prof. Daniel Fürth
Uppsala University, Sweden
Webpage: https://www.furthlab.xyz
Topic of the talk: A chemoselective in vivo sequencing chemistry
Abstract: To observe and perturb biological events at the single-molecule level directly in living systems as they naturally occur and unfold is the ultimate goal for any technique in the life sciences. I will present a new method for determining nucleotide sequences in nucleic acids directly in living cells. It is similar to primer extension by chemical ligation but makes use of a novel non-enzymatic, bioorthogonal, chemistry that acts as a specific fluorogenic activator with single-nucleotide fidelity. The technique has been applied to the tracking of individual mRNA transcripts in living cells with subcellular single-molecule resolution. To be able to directly interrogate single biomolecules in living systems, without the need for transgenics, opens up unprecedented capabilities to understand these systems at a level previously not possible.
Prof. Per Arvidsson
Karolinska Institutet, SciLifeLab DDD
Webpage: https://www.researchgate.net/profile/Per-Arvidsson-2
Topic of the talk: Explorations and innovations at the academia-industry interface - tales from the SciLifeLab DDD infrastructure
Abstract: SciLifeLab DDD - the national Swedish infrastructure for early drug discovery - transforms research at the interface of academia and industry. By supporting academic discoveries with industry standard infrastructure and expertise SciLifeLab DDD promotes the translation of research into therapeutic innovations. In order to meet the requirements of tomorrows healthcare, SciLifeLab DDD also explore and implement new drug discovery technologies such as DNA encoded chemical libraries, therapeutic oligonucleotides, proximity inducing agents including protein degraders. This talk will tell some of those tales…