My lab is focused on studying the structures, mechanisms and interactions of aggregating proteins. We are particularly interested in a certain fibre-like structure that is formed by a great variety of proteins called amyloid fibrils. We study amyloid proteins involved in disease, including Alzheimer's disease and motor neuron disease, as well as those that have functions in important biological processes.
The kinds of questions we are looking at include:
1) What are the functions of amyloids and aggregates in different biological processes?
2) What are the structural details of aggregates that have functional and disease-relevant roles?
3) How do other proteins and small molecules affect the aggregation of disease-relevant proteins, and at what stage do they affect aggregation? 4) What sequences are important for aggregation processes, and how can these be interfered with?
5) How do disease mutations affect aggregation or functional behaviour of aggregation-prone proteins?
We studying these topics with a range of structural and biophysical techniques including NMR spectroscopy (both solid-state and solution state), fluorescence-based aggregation assays, electron microscopy.
- Ball SR., Pham CLL., Lo V., Morris VK., Kwan AH. and Sunde M. (2020) Formation of Amphipathic Amyloid Monolayers from Fungal Hydrophobin Proteins. 2073: 55-72. http://dx.doi.org/10.1007/978-1-4939-9869-2_4.
- Göbl C., Morris VK., van Dam L., Visscher M., Polderman PE., Hartlmüller C., de Ruiter H., Hora M., Liesinger L. and Birner-Gruenberger R. (2020) Cysteine oxidation triggers amyloid fibril formation of the tumor suppressor p16INK4A. Redox Biology 28 101316: 101316-101316. http://dx.doi.org/10.1016/j.redox.2019.101316.
- Brender JR., Ghosh A., Kotler SA., Krishnamoorthy J., Bera S., Morris V., Sil TB., Garai K., Reif B. and Bhunia A. (2019) Probing transient non-native states in amyloid beta fiber elongation by NMR.. Chem Commun (Camb) 55(31): 4483-4486. http://dx.doi.org/10.1039/c9cc01067j.
- Cristóvão JS., Morris VK., Cardoso I., Leal SS., Martínez J., Botelho HM., Göbl C., David R., Kierdorf K. and Alemi M. (2018) The neuronal S100B protein is a calcium-tuned suppressor of amyloid-β aggregation.. Sci Adv 4(6): eaaq1702. http://dx.doi.org/10.1126/sciadv.aaq1702.
- Sun Y., Medina-Cruz A., Hadley KC., Galant NJ., Law R., Vernon RM., Morris VK., Robertson J. and Chakrabartty A. (2018) Physiologically Important Electrolytes as Regulators of TDP-43 Aggregation and Droplet-Phase Behavior. Biochemistry http://dx.doi.org/10.1021/acs.biochem.8b00842.