[Demelerlab] Reminder for Tomorrow's seminar by Dr. Vanessa Morris from New Zealand

[Borries Demeler]

Dear Colleagues,

It is my pleasure to invite you to a seminar from Dr. Vanessa Morris from
the University of Canterbury in Christchurch, New Zealand, on July 2nd,
1:00 pm, Room SA6010

* Title: **Cysteine oxidation triggers amyloid fibril formation of the
tumor suppressor p16*

p16INK4A (p16 for short) is a tumour suppressor protein that blocks cell
division and is found to be mutated in many cancers. We discovered that
under oxidizing conditions, the single cysteine residue of p16 forms an
intermolecular disulfide bond. Formation of the disulfide-linked dimer
leads to a dramatic structural rearrangement of the protein, from an all
alpha-helical structure to beta-sheet fibrils. These structures have
typical features of amyloid fibrils, a structure more commonly associated
with neurodegenerative diseases. The amyloid formation of p16 abolishes its
native function and therefore p16 amyloid formation may be a novel
regulatory mechanism of p16 activity. As the first of its kind, the formed
amyloids rely on the presence of the disulfide bond; exposure to reducing
agents disassembles the amyloids and p16 returns to its native, functional
state. We are currently investigating the structure, formation, and
disassembly mechanisms of the redox-regulated p16 amyloid fibrils, using a
range of molecular and cellular methods. This includes analytical
ultracentrifugation to characterize intermediates and aggregation pathways.
These findings will give insight into a novel disulfide-linked amyloid
structure, as well as highlighting their potential role in cancer and cell
division mechanisms.

Vanessa Morris is a senior lecturer at the University of Canterbury in
Christchurch, New Zealand, where she leads a protein biophysics and
structural biology research group focused on studying the structures,
mechanisms, and interactions of aggregating proteins. She obtained her PhD
from the University of Sydney before carrying out postdoctoral research at
the Technical University of Munich and the University Health
Network/University of Toronto, and then starting her current position in
2019. Vanessa’s group studies amyloid proteins involved in disease,
including Alzheimer's disease and cancer, as well as those with important
biological functions in a variety of organisms, using a range of methods
including NMR spectroscopy and electron microscopy.

There will be time to meet with our guest before or after the seminar.
Please send interest and availability to Heather Weiler to coordinate.

Looking forward to seeing you at the seminar!

-Borries
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