Mathias Lösche-Dept of Physics - Carnegie Mellon University

Mathias Lösche

Professor of Physics, Professor of Biomedical Engineering; NIST Associate

Office: Wean 6311
Phone: 412-268-2735
Fax: 412-681-0648

Education

Ph.D., Technical University of Munich

Research

In the past few decades, biology has revolutionalized our understanding of how living matter organizes itself to achieve the most astounding feat on the planet: Create intricate, organized structures that self-replicate and continuously develop further - despite the dictum of entropy which inequitably favors disorder over order. Are living systems therefore somehow miraculously exempt from the laws of Physics? - No, they have "learned" to exploit loopholes in the dictate of entropy in truly stunning ways! Biological Physics is a fascinating branch of "mainstream Physics" that tries to solve the underlying puzzles.

Our work in Experimental Biophysics focuses on the functional, structural and dynamic characterization of biomimetic membranes (that is, artifical and lipid bilayer systems that are simpler than complex biological membranes but capture their fundamental Physics aspects). For example, we use surface-sensitive x-ray and neutron scattering alongside with electrochemical and advanced optical techniques to identify, characterize, and optimize membrane models in which we study the association of proteins with lipid bilayers. Microscopy techniques are used to assess their in-plane fluidity, dynamics, and 2D morphology. With this set of tools, we investigate experimentally the physical principles of membrane self-assembly and functionality. We also study the molecular origins of disease, through quantification of the membrane interactions of proteins and peptides, such as neurotransmitters, toxins or tumor suppressor proteins. These studies contribute to a deeper understanding of disease mechanisms, cellular attack through pathogens and the self-assembly of viral particles, such as HIV, in affected cells.

Projects

Active

2013–2018      NIST-MSE 70NANB13H009, Innovative Neutron Metrology for the Study of Biomembranes in Health and Disease, PI: Lösche, US$ 1,146,826.

Goals:        Study biomembranes in their physiologically relevant, locally disordered state and develop metrology for their characterization with neutron scattering on the Ångstrom lengthscale.

2011–2016      NIST-MSE 70NANB11H139, Structure and assembly of membrane-associated proteins, PI: Lösche,  US$ 650,000.

Goals:        Develop neutron reflection metrology at the NIST Center for Neutron Research for the investigation of protein-membrane interactions.

2012–2016      NIH 1R01 GM101647, Membrane coupling and dynamic reorganization of Gag in viral budding, PI: Lösche, US$ 1,163,180.

Goals:        Determine the factors that control the association of the Gag MA domain with membranes in binding studies and reveal the mechanisms that lead to the recruitment of specific lipids into the viral shell. Characterize the origin and the implications of the conformational reorganization of full-length Gag at membrane surfaces in experimental and computational studies.

Pending

2016–2020      NIH 1R01 GM118870, PTEN Signaling: Membrane Association as a Function of Protein Status, PI: Lösche, US$ 1,500,966.

Goals:        Develop models of the mode of action of the PTEN tumor suppressor as an antagonist of PI3K in the PI3K/Akt pathway. This research will advance our understanding of cancer development and is likely to promote the development of new therapies based upon PTEN-L, a recently discovered secreted form of PTEN.

2016–2021      NIH 1R01, Structure, Dynamics and Function of Membrane-Associated Src-Family Tyrosine Kinases, PI: Roux, US$ 3,807,736. Role: Co-I

Goals:        Develop a fundamental understanding of the SH4-U region of SFKs—a critical element for controlling both the membrane localization and specificity toward downstream targets—that is likely to lead to the discovery of new intermediates states and alternate inhibitory strategies of kinase activities for drug development.

(as of June, 2016)

Publications

Selected Publications

  • Yang Shen, Marilia Barros, Tarek Vennemann, D, Travis Gallagher, Yizhou Yin, Sara B. Linden, Ryan D. Heselpoth, Dennis J. Spencer, David M. Donovan, John Moult, Vincent A. Fischetti, Frank Heinrich, Mathias Lösche, and Daniel C. Nelson, PlyC, a bacteriophage endolysin that is internalized by epithelial cells and retains bacteriolytic activity against intracellular streptococci, eLife 5, e13152 (2016)
  • Marilia Barros, Frank Heinrich, Siddhartha A. K. Datta, Alan Rein, Ioannis Karageorgos, Hirsh Nanda, Mathias Lösche, Membrane binding of HIV-1 matrix protein: Dependence on bilayer composition and protein lipidation, J. Virol. 90, 4544 (2016)
  • Robert A. Dick, Marilia Barros, Danni Jin, Mathias Lösche, Volker M. Vogt, Membrane binding of the Rous sarcoma virus Gag protein is cooperative and dependent on the SPA domain, J. Virol. 90, 2473 (2016)
  • Frank Heinrich, Srinivas Chakravarthy, Hirsh Nanda, Antonella Papa, Pier Paolo Pandolfi, Alonzo H. Ross, Rakesh K. Harishchandra, Arne Gericke, Mathias Lösche, The PTEN tumor suppressor forms homodimers in solution, Structure 23, 1952 (2015)
  • Frank Heinrich, Mathias Lösche, Zooming in on disordered systems: Neutron reflection studies of proteins associated with fluid membranes, Biochim. Biophys. Acta 1838, 2341 (2014)
  • Rima Budvytyte, Gintaras Valincius, Gediminas Niaura, Vladislava Voiciuk, Mindaugas Mickevicius, Hilary Chapman, Haw-Zan Goh, Prabhanshu Shekhar, Frank Heinrich, Sishharth S. Shenoy, Mathias Lösche, David J. Vanderah, Structure and properties of tethered bilayer lipid membranes with unsaturated anchor molecules, Langmuir 29, 8645 (2013)
  • Siddharth S. Shenoy, Hirsh Nanda, Mathias Lösche, Membrane association of the PTEN tumor suppressor: Electrostatic interaction with phosphatidylserine-containing bilayers and regulatory role of the C-terminal tail, J. Struct. Biol. 180, 394 (2012)
  • Prabhanshu Shekhar, Hirsh Nanda, Mathias Lösche, Frank Heinrich, Continuous distribution model for the investigation of complex molecular architectures near interfaces with scattering techniques, J. Appl. Phys. 110, 102216 (2011)
  • Peter N Yaron, Brian D Holt, Philip A Short, Mathias Lösche, Mohammad F Islam, Kris Dahl, Single wall carbon nanotubes enter cells by endocytosis and not membrane penetration, J. Nanobiotech. 9, 45 (2011)
  • Stephen A. Holt, Anton P. Le Brun, Charles F. Majkrzak, Duncan J. McGillivray, Frank Heinrich, Mathias Lösche, Jeremy H. Lakey, An ion-channel-containing model membrane: structural determination by magnetic contrast neutron reflectometry, Soft Matter 5, 2576 (2009)