Swedish Foundations’ Starting Grant Fellows

Department of Medical Biochemistry and Cell biology, University of Gothenburg
Project title: Structures of intramembrane receptor complexes: capturing transient GPCR dimers
Funded by: Ragnar Söderbergs stiftelse

Following a successful postdoctoral stint in the USA that lead to several extensive studies in the journal Nature, Linda Johansson recently returned to the University of Gothenburg to continue her path as lead researcher. Johansson is a medical structural biologist who develops pioneering microscopic methods to study the interaction between receptors for the hormone melatonin in our brain. This research may prove helpful in developing more effective methods and medicines for the treatment of type-2 diabetes and sleep difficulties.

Learn more: Research page at the University of Gothenburg
Photo: Elin Lindström. © Göteborgs universitet 2020.


Department of Experimental Medical Science, Lund University
Project title: Cerebrospinal fluid-mediated clearance of the brain
Funded by: Olle Engkvists stiftelse

At the Biomedical Center in Lund, Iben Lundgaard leads a lab conducting translational studies of the human glymphatic system, a recently discovered network of vessels that serves to clear our brain of waste in the form of dissolved substances and proteins. Disruptions to our glymphatic system can increase the risk of central nervous system damage and the development of neurodegenerative diseases such as Alzheimer’s disease; Lundgaard’s studies can potentially contribute to novel discoveries for improved brain health of great benefit to a large group of affected patients.

Learn more: Research page, Lund University
Photo: Tekla Kylkilahti 2020.

Department of Physiology and Pharmacology, Karolinska Institutet
Project title: The rewiring of the connectome in adolescence as a target for preventing schizophrenia
Funded by: The Erling-Persson Family Foundation

Sellgren Majkowitz leads a research group that develops and studies cellular models to better explain and predict the breakdown of nervous synapses, which has been observed in the brains of sufferers of schizophrenia. The psychiatric disease usually develops in late adolescence and the research group is well on its way to contributing to novel treatments that could be deployed early on for those at high genetic risk of disease onset.

Learn more: Research page at Karolinska Institutet
Photo: Ada Trepci. © Karolinska Institutet 2019.

Department of Cell and Molecular Biology / Department of Biosciences and Nutrition, Karolinska Institutet
Funded by: Ragnar Söderbergs stiftelse
> Presentation / Q&A  

Our bodies rely on tubes – tubes transport blood around our bodies, food through the digestive canal, and air in and out of our lungs. In our livers, tubes collect bile produced by liver cells and bring it to our digestive canal to help us digest fat and absorb nutrients. Tubes are essential: when they form badly during embryonic development in the womb, this leads to various diseases. Understanding how different organs take shape and build tubes is essential for developing therapies for these diseases.

Our project aims to uncover the mechanisms controlling liver bile duct development. We developed a mouse model for the bile duct disorder Alagille syndrome and using this model, together with samples from patients with Alagille syndrome, we identified new signals during liver development which we hypothesize control bile duct formation. We will thoroughly test the roles of the newly identified signals using genetic, surgical, and pharmacological approaches, and are establishing a new technique to manipulate gene expression in developing mouse liver – a technique which would reduce the numbers of animals used in science.

This project brings together tools from neuroscience, vascular biology, hepatology and developmental biology to address how tubes form during development. By resolving this question, we aim to understand a fundamental step in establishing a body plan, and in more practical terms we aim to re-introduce the missing signals and ultimately treat disorders such as Alagille syndrome.

Department of Physics, Stockholm University
Funded by: Ragnar Söderbergs stiftelse

Water is the most important liquid for life on Earth. Although a water molecule is apparently simple, the hydrogen-bonded network keeping these molecules together and determining the many anomalous macroscopic properties of water, is still a puzzle. Among different scenarios proposed to explain the anomalies in water, the most controversial issue is the hypothetical existence of two distinct liquid states: high- and low-density liquid (HDL, LDL). At ambient conditions the two structural components making up the two liquids fluctuate and cannot be studied as separate states. Rapid cooling of liquid water forms a low-density amorphous ice (LDA). High-density amorphous ice (HDA) can be made instead by pressure-induced amorphization of crystalline ice. A fascinating question arises: are the two amorphous ices the counterparts of the two proposed liquids states?

Modern X-ray scattering methods provide powerful tools to investigate both static structure and structural dynamics on different length- and timescales. Using X-rays, we have recently shown the diffusive character of HDL and LDL around their proposed glass transition temperatures at ambient pressure, but studies at elevated pressures are missing and challenging. This project aims to develop new experimental in situ pathways to study the pressure dependence of the hypothesized glass-to-liquid transition in amorphous ices. The experiments will have a high impact on the debate about different models explaining water´s mysteries.

Department of Medical Biochemistry and Biophysics, Umeå University
Funded by: Kempestiftelserna

Multidrug resistance in bacteria, originating from conjugative gene transfer, is an increasingly common problem in today’s world. The majority of bacteria that causes hospital infections are of gram-positive origin, but so far very little is known about their conjugation systems.

The goal of this project is to determine the molecular structure and function of conjugation complexes belonging to Type IV Secretion Systems (T4SSs) from gram-positive bacteria. This will lead to a deeper insight into one of the main processes responsible for horizontal gene transfer events, including the spread of antibiotic resistance genes in bacteria. It will also pave the way for future drug discovery against this type of bacteria, which are often involved in hospital infections. The proteins involved in forming the T4SS will be studied biochemically, structurally and biophysically. Since gram-positive T4SSs are very dissimilar from their gram-negative counterparts, little can be deduced from the few gram-negative systems so far studied. Furthermore, they occur in a number of pathogens. Another aspect that makes gram-positive T4SSs interesting is that they are used to efficiently transfer not only antibiotic resistance, but also virulence factors. This makes them attractive targets for the development of novel anti-virulence drugs, since deactivation of T4SSs would lead to attenuation of the pathogen followed by easier clearance of an infection by the host immune system.

Department of Physics, Lund University
Funded by: Olle Engkvists Stiftelse

Extreme bursts of radiation has enabled for measurements of coherent electron wave packet motion and photoionization delays from different microscopic targets. As electrons are the fastest receptors of electromagnetic forces at our disposal, I ask the question how precise pulse characterization can be achieved when the burst duration is comparable, or even below, the natural electron time scale?

I will regard coherent bound electron wave packets in atoms as super-accurate clocks that allow for direct measurements of the temporal structure of extreme bursts of short-wavelength radiation. During this project, I wish to study both the physics and applications of bound electron wave packets in three main activities: [A] preparation and optimization of coherent electron wave packets, [B] photoionization dynamics and interferometry of correlated electron wave packets and [C] coherent wave packet dynamics in a macroscopic (complex) environment.

I will develop novel numerical tools for extreme light-matter interaction including the first relativistic time-dependent configuration-interaction-singles method and the first correlated atomic calculations coupled to macroscopic wave equations at short wavelengths.

A successful project will greatly enhance basic knowledge of extreme light-matter interaction on the attosecond time scale and yield increased precision in pulse characterization that will open up new possibilities in future high-gain experiments in physics, chemistry and material science, where pump-probe experiments at short wavelengths will become an important new research direction. The assessment of all attosecond effects and the transition towards single-shot pulse analysis, required for free-electron-laser pulses, is the grand motivation for this proposal.

Department of Medicine Huddinge, Karolinska Institutet
Funded by: Familjen Erling-Persons Stiftelse

Inflammatory bowel disease (IBD) constitutes an increasing global health burden, yet effective treatments are lacking. Hampering rationale treatment strategies, the human intestinal immune system remains largely unexplored.

I have made seminal contributions to the discovery and characterization of innate lymphoid cells (ILCs) revealing that in addition to antigen-specific adaptive T cells, innate equivalents play important roles in mucosal immunity. Determining the complementarity and redundancy of these two lymphocyte systems, acting in concert, is important for our understanding of inflammatory diseases and the development of novel therapies.

I have access to unique patient samples as well as established methods for single-cell RNA-sequencing to perform a comprehensive molecular dissection of the human intestinal lymphocyte compartments in IBD. I will determine parallels between known, and identify novel, subsets of tissue-resident, inflammation-associated, innate and adaptive lymphocytes. Building on this unprecedented molecular characterization, we will take on some of the most pressing clinical problems in IBD by performing longitudinal assessments of intestinal lymphocytes from IBD patients on conventional and biological treatments. As only a fraction of patients respond to treatment, this approach provides an opportunity to unveil immunological signatures of treatment response and “drug-induced transformation” of inflammation in non-responders. Furthermore, we will unfold critical disease mechanisms and reveal novel therapy targets and how they can be used to personalize treatment.

Department of Political Science, Lund University
Funded by: Riksbankens Jubileumsfond
The over-arching objective of this project is to develop a new conceptualization of peace. The project claims that the possible success of peace processes depends on the extent to which they can tame and foster long-standing violent conflicts into inclusive and plural dialogic interactions among the citizens – suppressing and channeling – although not eradicating conflict. The project advances a conceptual framework where institutional inclusion and identity-change are the two central pillars by which peace is measured. The main endeavor for this project is to advance the concept of agonistic peace, which was developed in the field of international political theory, and to this date it has never been applied in empirical research. The concept will be developed for analyses of inclusion and plurality in peace processes, which can contribute with the generation of peace of a more sustainable nature. This project thus takes on the task of reconceptualising peace, creating an analytically rigorous, yet context-dependent understanding of peace, serving as a spring-board for new and more sustainable peace practices. The project conducts a comprehensive study of the Colombian, Israeli-Palestinian and Northern Ireland peace processes, which will be investigated in order to test the hypothesis and suggest new ways forward in terms of making peace processes more agonistic. Through a mixed-methods design, and an innovative and ambitious combination of interviews, institutional ethnography and quantitative analyses of survey material in order to probe the research questions, the project aims for far-reaching societal impact.
Department of Chemistry and Chemical Engineering, Chalmers University of Technology
Funded by: Familjen Erling-Perssons stiftelse
Imagine that you would measure the average eye colour of the population in Sweden. Clearly it would not say much about the colours of the eyes of the inhabitants. To acquire this information one must of course study them individually. The same holds true for complex biological molecules, especially proteins, which may exist in many different subpopulations that cannot be resolved in an ensemble measurement. Heterogeneities in biomolecular structure and function limit our understanding of biology and to advance further it is vital to be able to study single biomolecules. For proteins this is highly challenging since it must be done in a non-invasive manner, preferably while keeping them free in solution under physiological conditions.

The SIMONANO project (Single Molecule Analysis in Nanoscale Reaction Chambers) aims to develop new platforms for single protein analysis which provide essential advantages. Molecules will be entrapped in gated nanoscale reaction chambers, thereby eliminating the need of field gradient forces or surface immobilization. Further, the molecules can be entrapped at physiological ionic strength, pH and temperature. Most importantly, because the gates to the reaction chambers can be individually controlled and allow liquid to pass, it will be possible to lure molecules into the chambers by hydrodynamic forces. This should make it possible to not only entrap but also to mix individual molecules with each other. Advanced fluorescence microscopy will be used to detect the proteins and their reactions.

The impact of being able to study individual proteins and even protein pairs in a reliable non-invasive manner opens up for great scientific advancements in life science. Once developed and evaluated in this project, it can be envisioned how the nanoscale reaction chambers are distributed to and used by molecular biologists worldwide, which will greatly contribute to advancing our understanding of life on the molecular level. This will, in turn, lead to improved applications in biotechnology and medicine.

Department of Mathematics, Uppsala University
Funded by: Ragnar Söderberg foundation
My focus is on random graphs, a research area in the intersection between probability theory and combinatorics. This is one of the most dynamic fields in mathematics with many interesting “pure” mathematical questions as well as important applications in e.g. computer science, physics, bioinformatics and communication reliability (e.g. the Internet). Random graphs are graphs generated by random processes describing how the vertices are connected to each other through edges. I have a special interest in random trees. Trees are connected graphs without cycles, and random trees have become an increasingly hot area due not least to their importance for algorithms in computer science.
My goal is to advance the field of random graphs, especially random trees. By introducing novel methods into the field, alone and in combinations, and using these methods I aim to obtain general results valid for whole classes of random graphs. A special ambition is to combine probabilistic methods, such as Pólya urns, branching processes, Stein’s method with couplings, and renewal theory with innovative combinatorial approaches to solve important problems.
Three main topics will be addressed:
1. Random trees, with a focus on the study of fringe trees as a novel approach to obtain general results for whole classes of random trees;
2. Percolation theory, especially bootstrap percolation, for studies of mathematical “infectiosity” in graph networks (with broad applications in e.g. physics, biology and epidemiology); and
3. Random networks, specifically (i) the configuration model (an important random network model due to its proven usefulness for studying various real world networks in e.g. biology and sociology); (ii) CTM protocols (commonly used to avoid collisions in e.g. radio, electricity and internet communications); and (iii) stochastic block models (that have become increasingly important in biological and sociological research on community interactions).
Department of Physics, Lund University
Funded by: Stiftelsen Olle Engkvist byggmästare
SFSG Fellow in 2017, ERC StG awarded starting from 2019
In this project I will develop ultra-high resolution X-ray detectors based on semiconductor nanowires, whose spatial resolution will be radically better than the current state of the art. In X-ray detectors the primary X-ray absorption induces a cascade of secondary electrons and photons, which are measured at the front or back of the detector, but during the long transport to the point of detection these can spread orthogonally to the optical axis. This limits the resolution in present bulk detectors.

My novel concept is to create a nanostructured detector based on an array of semiconductor nanowires, which will confine and physically prevent spreading of the secondary electrons and photons. In a nanowire array, the pixel size is the diameter of the nanowire, which can be as low as 10 nm, while the nanowires can be as long as the X-ray absorption length. The very high aspect ratio of nanowires allows detectors with simultaneously very high spatial resolution and sensitivity. I will investigate both direct detectors and scintillators, in which the secondary electrons and photons are detected, respectively.

The objective is to create detectors based on arrays of 10 nm-diameter nanowires. Imaging experiments will compare these two types with each other and with commercial detectors. Time- and temperature resolved measurements will be used to improve understanding of the X-ray physics in these nanodevices, with strong quantum confinement of electrons and phonons and high surface to volume ratio. This novel detector concept can be used for high-resolution imaging of samples on the nanoscale, maintaining the unique ability of X-rays to study samples in realistic conditions: DNA within live cells, the strained channel in single operational transistors or individual nanoparticles in a charging battery. High resolution detectors could also be employed in X-ray spectroscopy and diffraction.

Division of Molecular Hematology, Lund University
Funded by: Familjen Erling-Perssons stiftelse
This proposal aims to unravel a completely new facet of gene expression governed by RNA pseudouridylation (Ψ), the most abundant single nucleoside RNA modification in living organisms, which directly impacts the stem cell transcriptome during normal and malignant hematopoiesis. Importantly, RNA modification is newly emerging as a key mechanism to coordinate gene expression in stem cells. Recent data show that Ψ modifications are dynamic and widespread among RNAs in cells and tissues, suggesting that Ψ may rapidly rewire a cell’s transcriptome. This proposal will be transformative in hematopoietic research by defining for the first time a new RNA-pseudouridylation ‘code’ that drives distinct genetic programs in stem and cancer cells.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet
Funded by: Ragnar Söderberg foundation
I will use novel genome-wide approaches to investigate the transcriptional basis of the non-genetic heterogeneity driving divergent gene expression responses within a clonal population using S. cerevisiae. This research has a dual objective: 1) to refine our knowledge of translation regulation and its contribution to cell-to-cell variability, and 2) to develop novel genome-wide approaches to functionally characterize and assign molecular and cellular phenotypes to subtle variations of the transcriptome. These approaches will be complemented by analysing the molecular phenotypes of the mRNA isoforms (e.g., association to ribosomes or RNA binding proteins). This will allow linkage of molecular phenotypes with cellular consequences, and highlight those variations with higher functional potential. Once I identify novel mechanisms implicated in the appearance of phenotypically divergent cells, I will characterize selected targets using biochemical and molecular biology tools.
Department of Chemistry and Molecular Biology, University of Gothenburg
Funded by: Ragnar Söderberg foundation
SFSG Fellow in 2015, ERC StG awarded starting from 2018
The research project aims to master the energy pathways in electronically excited molecules. Doing so is of fundamental importance in lighting technologies, which today consumes around 20% of all produced electricity in the world. In a modern lighting device such as a mobile phone screen, electricity is used to create electronically excited molecular states. We will develop molecular systems enabling the conversion of these excited states into light as efficient and fast as possible. Thus facilitating for a new generation of energy efficient lighting devices.
Department of Physics and Astronomy, Uppsala University
Funded by: Ragnar Söderberg foundation
My research strives towards obtaining better mathematical descriptions for high-energy collisions (scattering amplitudes) between elementary particles or even strings. New mathematical formulations of fundamental processes can lead to a better understanding of the theories that describe our universe: e.g. the theory of gravity and other established theories known as gauge theories — describing the strong and electroweak forces of the Standard Model of particle physics. By studying the mathematical details of scattering amplitudes in these theories, I have found that there exists an underlying Lie algebra that controls the kinematical variables. However, as of today, no complete mathematical description of this algebra is known. A goal of my research is to find this complete description.
Department of Molecular Hematology, Lund University
Funded by:Familjen Erling-Perssons stiftelse
SFSG Fellow in 2015, ERC StG awarded starting from 2017
The vertebrate immune system has evolved for hundreds of millions of years into a balanced and self-regulatory system encompassing a wide spectrum of cell types that act in concert to protect us from infections. Most of what we know about the formation of the immune system comes from studies in adults but much less is known about the coordinated series of events that build up the immune system from scratch in the developing fetus. Mutations occurring before birth in immune cells of the developing baby remain the main cause of cancer related deaths in children. Cancers of the immune system, leukemia, are furthermore of different kinds in infants and children compared to adults. These and other clues suggest that fetal immune development may be significantly different from that in adults. In the project FatemapB, we will use two advanced tracking technologies to follow the behavior of fetal and adult immune cell development. The state-of-the-art strategies will allow for the high-resolution visualization of how a diverse immune system is first formed in the fetus and then maintained throughout adulthood. Extending beyond normal development, this work has important clinical implications to improve our understanding of fetal specific leukemia. Finally, we have developed a technology to reinitiate fetal like immune development in adult blood stem cells and will within the scope of FatemapB explore the ability of this technology to improve immune regeneration following bone marrow transplantation treatments.
Joan Yuan, foto: Wallenberg.com
OKSANA MONT (Consolidator grant)
International Institute for Industrial Environmental Economics, Lund University
Funded by: Riksbankens Jubileumsfond
Urban sharing of assets, spaces and skills has emerged as a prospective solution to sustainability challenges faced by cities. However, its sustainability potential and institutional processes to harness it have not been systematically scrutinized. This ambitious research programme aims to examine, test and advance knowledge about design, sustainability of practices and institutionalisation processes of urban sharing organisations across 8 cities from 5 continents. The research conflates studies on sustainable consumption and production with organisational theory and the neo-institutional field.The three objectives are: 1. Design: To examine the ways in which urban sharing schemes are designed and how they vary across cities. 2. Practices: To study the sustainability of daily practices of urban sharing schemes and why and how they vary in different cities. 3. Processes: To develop and test a theoretical framework for integrative and comparative assessment of institutionalisation processes of urban sharing schemes across cities.
ALBERTO VOMIERO (Consolidator grant)
Department of Engineering Sciences and Mathematics, Luleå University of Technology
Funded by: Kempestiftelserna
Exploiting solar light is one of the main challenges that could significantly contribute to solve the present world energy issues. The photovoltaic and the thermoelectric effects are among the most promising. The photovoltaic effect directly generates electric power after absorbing solar light, and the thermoelectric effect indirectly generates electric power after absorbing heat from the Sun. The project aims at investigating a new way to exploit solar radiation, by combining the photovoltaic and thermoelectric effects using nanowire arrays (very similar to a miniaturized grassland). The idea is to absorb both the visible and the infrared part of the solar spectrum (which we cannot see with our eyes, but still is there) using a composite nanostructure. In our scheme, the two processes will occur simultaneously, improving the efficiency of the conversion from light to electric power, towards a “panchromatic” absorption of Sun light. The project is based on the very peculiar optical and electrical characteristics of materials at nanoscale, organized in arrays of nanowires. We aim at solving the intrinsic limitations of the photovoltaic and thermoelectric processes: poor matching between the absorption properties of solar cells and the different “colors” forming the full spectrum of the Sunlight, and the low density of electric charges in thermoelectric devices.
Alberto Vomiero, foto: Ted karlsson