【For INTERNATIONAL COLLABORATIVE RESEARCH 2017】

SUMMARY of

DATE: 21 May, 20182017 RESEARCH RESULTS REPORTFor International Collaborative Research with IPR, Osaka University
Research Title

A closer look into the mechanism of κ-casein fibril formation

Applicant

Name

CARVER, John Adrian

Affiliation

Research School of Chemistry, The Australian National
University, Canberra, Australia

Present Title

Professor and Director of the Research School of Chemistry

Research Collaborator (Host PI)

GOTO, Yuji

Summary
Alzheimer’s, Parkinson’s, and Huntington’s diseases are age-related, neurodegenerative
diseases associated with the deposition in the brain of highly ordered protein aggregates termedamyloid fibrils. Despite this connection, it has been difficult to establish a causative link between
the formation of amyloid fibril deposits in neural tissue and the onset and progression of neuraldecline. κ--Casein, a major milk protein, rapidly forms amyloid fibrils at physiological pH andtemperature following chemical modification. In our previous collaboration, we investigated theeffects of ultrasonication on fibril formation by micellar κ-casein. The aim of this project is toprepare and monitor fibril formation by monomeric κ-casein in the presence and absence ofultrasonication.
To perform the collaboration, Carver visited IPR from December 2 to 8, 2017 andBahraminejad, Elmira (PhD Candidate in Biochemistry) visited IPR from November 24 toDecember 19, 2017.
There are two cysteine residues in κ-casein. In an effort to elucidate the oligomer-fibriltransition, we used a cysteine-specific fluorescent probe to monitor the oligomeric state of κ-CN.
The utility of the probe was assessed by investigating the relationship between κ-CN’s oligomericstate and the fluorescein-associated fluorescence intensity. The results indicated that cysteinespecific fluorescent probe will be a promising approach to monitoring oligomerisation of κ-CN inorder to better understand the mechanism of its conversion into amyloid fibrils.
Carver is one of organizers of the Second Joint Symposium between the Institute for Protein
Research (Osaka University) and the Research School of Chemistry (Australian NationalUniversity) held December 3rd -5th, 2017 at IPR. Organizing Committee: John Carver, Yuji Goto,Damien Hall and Haruki Nakamura. Occasion: In 2015 the Research School of Chemistry (RSC) ofthe Australian National University signed an institutional linkage agreement with the Institute forProtein Research (IPR) of Osaka University in Japan. To mark this occasion a joint symposium washeld in Australia in November of 2015. To further cement the pairing of the two research institutes
a second RSC-IPR joint symposium was held in Osaka Japan, in late December, at the Institute forProtein Research.
With other international collaborators, we planned and applied for the JSPS Core-to-Core
Program, a program designed to create top world-class research centers, and the proposal has been
accepted. The program: “An international cutting-edge network for the study of protein aggregation”
will continue for 5 years (2017-2022) and we will advance our collaboration on κ-casein fibril
formation taking advantage of this program.