The philosophy of the quantum world, treatment options for multiple sclerosis, and a new class of RNA molecules: the European Research Council awards three prestigious grants to projects at LMU.
Philosopher Alyssa Ney, neuroimmunologist Martin Kerschensteiner, and chemist Thomas Carell have each been awarded an Advanced Grant by the European Research Council (ERC). The funding of up to 2.5 million euros supports highly innovative research projects that go beyond the current state of research and forge ahead into new research territories.
Prof. Dr. Matthias Tschöp, President of LMU, congratulates: “Today we really have reason to celebrate: Our university has secured three new ERC Advanced Grants at once! This is fantastic news and a great recognition of the outstanding research that is conducted here every day. My heartfelt congratulations go to Professor Alyssa Ney, Professor Thomas Carell, and Professor Martin Kerschensteiner, and their teams. With their ideas, creativity, and dedication, they contribute to us being at the forefront of science, making our university internationally visible, and continually exploring new interdisciplinary paths.“
The individual ERC-funded projects
On the nature of quantum reality
Professor Alyssa Ney is Chair of Metaphysics at the Faculty of Philosophy, Philosophy of Science and Religious Studies at LMU and member of the MCQST cluster of excellence.
Quantum technologies could soon become part of our everyday lives. But even 100 years after the founding of quantum physics, there is still no consensus on what it says about reality. Quantum phenomena such as entanglement call our conception of reality into question.
The role of the observer
In her new ERC project MetaQ – The Nature of Quantum Reality, Alyssa Ney aims to combine insights from physics and philosophy to forge a deeper understanding of the quantum world and our place within it. A central premise of the project is that consensus on the broader implications of quantum physics has been thwarted by fundamental disagreements about the role of the observer in physical theories.
This has caused philosophers to hesitate before taking the most influential interpretations of quantum mechanics among physicists seriously. While a prominent tradition going back to Albert Einstein holds that observers have no place in a fundamental physical theory, many physicists today believe that the reality described by quantum physics cannot be understood without ascribing a special role to observers.
The primary task of MetaQ is to precisely articulate the prevailing conceptions of quantum reality that place special emphasis on the role of observers. These go back to an idea by physicist John Wheeler that we live in a “participatory universe,” from which the concept of “it-from-bit” later emerged. Approaches of this kind include QBism and the information theoretical frameworks of Časlav Brukner, Markus Müller, and Anton Zeilinger.
MetaQ will provide the first comprehensive interdisciplinary metaphysical analysis and evaluation of these approaches. “Building on this, we want to develop an interpretation of quantum reality that can be used in metaphysics to advance work on several fundamental philosophical questions,” says Ney. These includes questions about the nature of physical reality, its relation to ourselves and our minds, and our status as free agents.
New targets for multiple sclerosis therapy
Professor Martin Kerschensteiner is Director of the Institute of Clinical Neuroimmunology and spokesperson for the Biomedical Center at LMU. He is also a member of the SyNergy Cluster of Excellence.
Multiple sclerosis (MS) is the most common cause of neurological disability in young adults. In this chronic inflammatory disease, the immune system attacks the brain and spinal cord, damaging nerve fibers. Myeloid cells such as macrophages, monocytes, and microglia are main effectors of tissue damage across disease stages. However, it is still poorly understood which signals control these cells.
Kerschensteiner wants to close this gap in our knowledge with his project TACO (Targeting myeloid cell states, actions and interactions in neuroinflammation) that aims to establish new strategies to leverage the potential of modern single-cell technologies: Instead of analyzing tissue only as a bulk average, scientists can use these tools to examine the genetic make-up and functional behavior of individual cells in detail. This allows them to capture complex disease processes with a level of precision that was previously unattainable. “I believe that if we want to unlock the true potential of the single-cell revolution for patients, we need to find new ways to interrogate cellular states, actions, and interactions at scale and in vivo,” emphasizes the neuroimmunologist.
Identifying promising signaling pathways of myeloid cells
The goal of his project is to enable efficient targeting of myeloid cells. In preparation, he has acquired highly-resolved datasets that allow him to capture the signals that myeloid cells receive across disease trajectories in MS. Now he wants to identify which of these signals are best suited as targets for therapeutic interventions.
Kerschensteiner and his team will begin by developing novel in-vivo CRISPR screening methods to systematically uncover the essential control mechanisms of myeloid cells in MS models. Next, they will combine CRISPR manipulations with single-cell analysis, multi-photon microscopy, and spatial transcriptomics to delineate how these signals define the cell states, functions, and interactions in the inflamed central nervous system. Finally, they will identify the signaling pathways best suited for therapeutic intervention based on their activity across various disease stages and lesion sites.
“The aim of TACO is to unlock the potential of existing and emerging (multi)omics datasets for the design of therapeutic interventions targeted to disease stages, lesion sites, and cellular states,” says Kerschensteiner. “We hope that this project will provide new approaches for the treatment of MS and build a versatile pipeline that can be readily adapted to other neurological conditions to which myeloid cells contribute.”
A new class of RNA molecules
Professor Thomas Carell is Chair of Organic Chemistry at LMU’s Institute of Chemical Epigenetics and a member of the NUCLEATE Cluster of Excellence.
RNA plays a key role in protein biosynthesis – the process by which genetic information in the cell is translated into functional proteins. It can both store genetic information and catalyze biochemical reactions. This makes the class of ribonucleic acids an important key to unlocking how life works at the molecular level. Recent research has shown that RNA is actually a good deal more versatile than previously thought and performs numerous additional functions, many of which are little researched or entirely unknown.
An often overlooked property of RNA, for example, is that in addition to the four ‘classic’ nucleobases – adenine, guanine, cytosine, and uracil – it contains around 170 further nucleosides that deviate from the standard structure. As the primary adapter molecules for translation, so-called transfer RNAs (tRNAs) possess the largest number of these non-canonical nucleosides. A surprising recent discovery showed that tRNAs can be split into smaller fragments – so-called tsRNAs – by partially unknown enzymes.
The role of non-canonical nucleosides
In the course of his ERC project RFrag – Synthesis and Function of Non-Canonical RNA Fragments, Thomas Carell plans to research which functions are performed by this newly discovered class of RNA molecules.
To answer this question, Carell’s team will start by specifically manufacturing the RNA fragments in the laboratory. For this purpose, the researchers are developing chemical building blocks to synthesize tsRNAs that also contain non-canonical nucleosides. Much of our knowledge about tsRNAs to date is based on synthetically manufactured RNA molecules that are lacking these unusual building blocks. What role the modifications play for the function of the fragments is therefore largely unexplained.
The researchers want to clarify how the RNA fragments are further processed by specific enzymes – and characterize the enzymes involved. Another central question of the project is whether and how tsRNAs and their cleavage products affect the immune system. Initial data suggest that the RNA fragments can trigger immune responses – possibly even ones that are relevant for defense against cancer cells.
Another focus is on tsRNAs from pathogenic bacteria: Many bacteria possess their own, characteristic non-canonical nucleosides. Carell’s team hypothesizes that precisely such structures trigger particularly strong immune responses. “Our work will not only furnish new insights into the biology of RNA,” says Carell, “but could also expand our understanding of how foreign-RNA and hence infections and tumors are recognized by the immune system, Particularly tumor-RNA varies dramatically from RNA of healthy cells regarding the content of modified nucleosides.”