Singapore, April 22, 2013 – Amyloids, or fibrous aggregates of abnormally folded proteins, are a common feature in degenerative diseases such as Alzheimer’s, diabetes and cancer. Amyloids occur naturally in the body, but despite decades of research, their mechanism of formation remains unknown, hampering drug development efforts. Now, a new class of ultrasmall peptides developed by the Institute of Bioengineering and Nanotechnology (IBN) offers scientists a platform for understanding this phenomenon, providing them with the insights required to design more effective treatments for these diseases.
IBN Executive Director Professor Jackie Y. Ying said, “Our researchers have been focusing on creating biomimetic materials for nanomedicine and cell and tissue engineering applications. The novel ultrasmall peptides developed by IBN are not only highly effective as synthetic cell culture substrates, but also as a model for studying the mystery of amyloid formation. Such fundamental understanding could contribute towards advancing medical treatment of amyloid-related disorders.”
First discovered in 2011 by IBN Team Leader and Principal Research Scientist Dr Charlotte Hauser, the peptides were formed from only 3-7 amino acids, making them the smallest ever reported class of self-assembling aliphatic compounds. Peptides perform a wide range of functions in the body, and are distinguished from proteins based on size. Building on this earlier research, IBN researchers have found a striking similarity between the structure of their synthetic peptides and the protein structure of naturally occurring amyloids in the latest study published in Proceedings of the National Academy of Sciences1.
Dr Hauser elaborated, “This is the first proof-of-concept that our peptides self-assemble in the same way as naturally occurring amyloid sequences. Knowing that the process of amyloid formation is common across various chronic degenerative diseases, our goal is to identify the specific trigger so that we can design the appropriate drugs to inhibit and control the aggregate formation.”
The IBN team collaborated with researchers from the Institute of High Performance Computing and the European Synchrotron Radiation Facility to validate their peptides with the core protein sequences of three diseases: Alzheimer’s, diabetes and thyroid cancer.
The results revealed that the mechanism behind the self-assembly of amyloids from smaller intermediate structures into larger amyloid structures was similar to how the IBN peptides were formed. In addition, this study supports the growing evidence that early intermediates are more toxic than the final amyloid fibers, and may even be the driving force behind amyloid formation.
Patent applications have been filed on this research, and the next step of this project is pre-clinical evaluation of ultrasmall peptide therapeutics. IBN will also investigate other amyloid disorders such as corneal dystrophy, which can result in blindness.
What are Peptides?
Peptides are short to medium length sequences of amino acids, differentiated from proteins based on their smaller size. In proteins, the molecules fold into a specific three-dimensional structure that influences its activity or function in the body. Amyloids comprise distinctly structured aggregates that are formed by functional, but also abnormally folded proteins in the body.
1. A. Lakshmanan, D. W. Cheong, A. Accardo, E. Di Fabrizio, C. Riekel and C. A. E. Hauser, “Aliphatic Peptides Show Similar Self-Assembly to Amyloid Core Sequences, Challenging the Importance of Aromatic Interactions in Amyloidosis,” Proceedings of the National Academy of Sciences 110 (2013) 519-524.,
2. C. A. E. Hauser, R. Deng, A. Mishra, Y. Loo, U. Khoe, F. Zhuang, D. W. Cheong, A. Accardo, M. B. Sullivan, C. Riekel, J. Y. Ying and U. A. Hauser, “Natural Tri- to Hexapeptides Self-Assemble in Water to Amyloid ß-Type Fibre Aggregates by Unexpected a-Helical Intermediate Structures,” Proceedings of the National Academy of Sciences, 108 (2011) 1361-1366.
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About the Institute of Bioengineering and Nanotechnology
The Institute of Bioengineering and Nanotechnology (IBN) was established in 2003 and is spearheaded by its Executive Director, Professor Jackie Yi-Ru Ying.
Professor Ying was a Professor of Chemical Engineering at the Massachusetts Institute of Technology (1992 - 2005). She was recognized as one of “One Hundred Engineers of the Modern Era” by the American Institute of Chemical Engineers in 2008 for her groundbreaking work on nanostructured systems, nanoporous materials and host matrices for quantum dots and wires.
Under her direction, IBN conducts research at the cutting-edge of bioengineering and nanotechnology. Its programs are geared towards linking multiple disciplines across engineering, science and medicine to produce research breakthroughs that will improve healthcare and our quality of life.
IBN’s research activities are focused in the following areas:
Nanomedicine, where functionalized polymers, hydrogels and biologics are developed as therapeutics and carriers for the controlled release and targeted delivery of therapeutics to diseased cells and organs.
Cell and Tissue Engineering, where biomimicking materials, stem cell technology, microfluidic systems and bioimaging tools are combined to develop novel approaches to regenerative medicine and artificial organs.
Biodevices and Diagnostics, which involve nanotechnology and microfabricated platforms for high-throughput biomarker and drug screening, automated biologics synthesis, and rapid disease diagnosis.
Green Chemistry and Energy, which encompass the green synthesis of chemicals and pharmaceuticals, catalytic conversion of biomass, utilization of carbon dioxide, and new nanocomposite materials for energy applications.
IBN's innovative research is aimed at creating new knowledge and intellectual properties in the emerging fields of bioengineering and nanotechnology to attract top-notch researchers and business partners to Singapore. Since 2003, IBN researchers have published over 860 papers in leading journals.
IBN also plays an active role in technology transfer and spinning off companies, linking the research institute and industrial partners to other global institutions. The Institute has a portfolio of over 620 active patents/patent applications, and welcomes industrial and clinical partners to collaborate on and co-develop its technologies. IBN has successfully commercialized 46 patents/patent applications, and has established 6 spin-off companies.
IBN's current staff and students strength stands at over 150 scientists, engineers and medical doctors. With its multinational and multidisciplinary research staff, the institute is geared towards generating new biomaterials, devices, systems and processes to boost Singapore’s economy in the medical technology, pharmaceuticals, chemicals, consumer products and clean technology sectors.
IBN is also committed to nurturing young talents. Besides the training of PhD students, IBN has a Youth Research Program (YRP) for students and teachers from secondary schools, junior colleges, polytechnics, and universities. Since its inception in October 2003, YRP has reached out to more than 61,900 students and teachers from 289 local and overseas schools and institutions. Over 1,690 students and teachers have completed research attachments at IBN for a minimum period of four weeks.
For more information, visit www.ibn.a-star.edu.sg.