Ana Teixeira Group
We are interested in understanding the roles of spatial organization in biological processes such as membrane receptor activation and signal propagation within and between cells. To this end, we develop new tools that enable manipulation and analysis of the spatial organization of biological systems from nanoscale to tissue levels. We aim to contribute to a new paradigm in drug development founded on the understanding of the biophysical context of target proteins.
Membrane proteins often display non-uniform, dynamic spatial distributions. However, we know surprisingly little about how the nanoscale spatial distribution of membrane proteins and their lateral mobility affect their functions. With most drugs targeting membrane proteins, there is a need to understand the modes of biophysical regulation of membrane proteins and to overcome methodological roadblocks to analysing and controlling the organization of membrane proteins at the nanometer to 100-nanometer lengthscale. We use DNA nanotechnology as a tool to achieve this due to its tailorability and precision.
We developed NanoDeep-a non-microscopy based super resolution method for unbiased analysis of protein nanoenvironments at the nanoscale that translates spatial organization information into a DNA sequencing readout. NanoDeep has the potential to provide a breakthrough in the analysis of the spatial distributions of hundreds of proteins simultaneously with super-resolution (Ambrosetti et al., Nature Nanotechnology, 2020).
We are addressing the hypothesis that the nanoscale spatial organization and lateral mobility of membrane receptors regulate their functions. We use DNA nanostructures as scaffolds that are modified with proteins at defined positions. Using this method, we found that the nanoscale spatial distribution of ephrin-A5 ligands regulates the levels of activation of EphA2 receptors and downstream signalling (Shaw, Lundin et al., Nature Methods, 2014; Verheyen, Fang, et al., Nucleic Acids Research, 2020).
To understand protein transport within single muscle cells and between muscle and other tissues, we use microfluidics and mathematical modeling. We found that the propagation of nuclear proteins within skeletal muscle cells could be predicted based on size, nuclear import speed, and ability to diffuse across the nuclear pore. Further, using a microfluidics model, we found that neurturin is a mediator of PGC-1α1-dependent retrograde signaling from muscle to motor neurons (Taylor-Weiner, Grigsby et al., PNAS, 2020; Mills, Taylor-Weiner et al, Molecular Metabolism, 2018).
- Novo Nordisk Foundation
- European Research Council Consolidator Grant
- Karolinska Institutet
- Knut and Alice Wallenberg Foundation
- Marie Curie Actions European Union H2020
- Swedish Research Council
- Human Frontier Science Program (HFSP) Young Investigator Grant Award
Spatial Regulation of T-Cell Signaling by Programmed Death-Ligand 1 on Wireframe DNA Origami Flat Sheets.
Fang T, Alvelid J, Spratt J, Ambrosetti E, Testa I, Teixeira AI
ACS Nano 2021 Feb;():
A DNA-nanoassembly-based approach to map membrane protein nanoenvironments.
Ambrosetti E, Bernardinelli G, Hoffecker I, Hartmanis L, Kiriako G, de Marco A, Sandberg R, Högberg B, Teixeira AI
Nat Nanotechnol 2021 Jan;16(1):85-95
Spatial organization-dependent EphA2 transcriptional responses revealed by ligand nanocalipers.
Verheyen T, Fang T, Lindenhofer D, Wang Y, Akopyan K, Lindqvist A, Högberg B, Teixeira AI
Nucleic Acids Res 2020 06;48(10):5777-5787
Modeling the transport of nuclear proteins along single skeletal muscle cells.
Taylor-Weiner H, Grigsby CL, Ferreira DMS, Dias JM, Stevens MM, Ruas JL, Teixeira AI
Proc Natl Acad Sci U S A 2020 02;117(6):2978-2986
Solution-Controlled Conformational Switching of an Anchored Wireframe DNA Nanostructure.
Hoffecker IT, Chen S, Gådin A, Bosco A, Teixeira AI, Högberg B
Small 2019 01;15(1):e1803628
Neurturin is a PGC-1α1-controlled myokine that promotes motor neuron recruitment and neuromuscular junction formation.
Mills R, Taylor-Weiner H, Correia JC, Agudelo LZ, Allodi I, Kolonelou C, Martinez-Redondo V, Ferreira DMS, Nichterwitz S, Comley LH, Lundin V, Hedlund E, Ruas JL, Teixeira AI
Mol Metab 2018 01;7():12-22
Spatial control of membrane receptor function using ligand nanocalipers.
Shaw A, Lundin V, Petrova E, Fördős F, Benson E, Al-Amin A, Herland A, Blokzijl A, Högberg B, Teixeira AI
Nat Methods 2014 Aug;11(8):841-6
CtBPs sense microenvironmental oxygen levels to regulate neural stem cell state.
Dias JM, Ilkhanizadeh S, Karaca E, Duckworth JK, Lundin V, Rosenfeld MG, Ericson J, Hermanson O, Teixeira AI
Cell Rep 2014 Aug;8(3):665-70
A 3D Alzheimer's disease culture model and the induction of P21-activated kinase mediated sensing in iPSC derived neurons.
Zhang D, Pekkanen-Mattila M, Shahsavani M, Falk A, Teixeira AI, Herland A
Biomaterials 2014 Feb;35(5):1420-8
Electrochemical control of growth factor presentation to steer neural stem cell differentiation.
Herland A, Persson KM, Lundin V, Fahlman M, Berggren M, Jager EW, Teixeira AI
Angew Chem Int Ed Engl 2011 Dec;50(52):12529-33