基本信息
浏览量:0
职业迁徙
个人简介
Research interests
The formation of stable, fibrillar protein assemblies is associated with many disease states, including Alzheimer's disease and Type II diabetes. These are non-functional deposits. Protein aggregates that have similar structural features but which are functional have been identified in several microorganisms. In these cases the self-assembly of the protein is advantageous to the organism. For example, hydrophobins are fungal proteins that self-assemble in an ordered manner into amphipathic films at air:water interfaces. They reduce the surface tension at air:water boundaries and form very hydrophobic coatings on fungal spore surfaces which facilitate dispersal in air. Hydrophobin assemblies share the ordered beta-sheet structural core that has been characterized in amyloid deposits.
Hydrophobin assemblies shield the human pathogenic fungus Aspergillus fumigatus from the immune response during infection, allowing this fungus to go on to cause life-threatening invasive aspergillosis. In rice blast, the most important fungal disease of rice, infection of the plants is facilitated by the production of a hydrophobin layer by the fungus Magnaporthe grisea. We are therefore interested in studying the biophysical and structural basis for the self-assembly of hydrophobins, with a view to understanding the role played by these proteins in fungal infections. Hydrophobin monolayer formation is a unique system that combines protein self-assembly with the generation of functional surfaces. These remarkable properties suggest a range of commercial applications, including biocompatibility enhancement of medical implants and emulsion and dispersion applications in foods and pharmaceuticals. This project involves using mutagenesis to probe the effect of sequence on hydrophobin structure and the study of the self-assembly process with techniques such as fluorescence, nuclear magnetic resonance, X-ray fibre diffraction and electron microscopy. Our work aims to develop a detailed picture of hydrophobin organisation within surface films. We hope to manipulate the self-assembly properties of the hydrophobins for the rational design of novel biological polymers and to design molecules that inhibit fungal spore dispersal and colonisation.
We have recently discovered that certain viral proteins can inhibit the host programmed cell death pathway necroptosis. This occurs by formation of heteromeric amyloids fibrils composed of both viral and host proteins that contain the amyloidogenic sequences known as RHIMs (RIP Homotypic Interaction Motifs). The Sunde group has applied single molecule methods to characterise these hetero-amyloids and to reveal this novel viral sequestration of host proteins and the molecular basis for viral inhibition of RHIM-based signalling in mammalian cells. This project aims to investigate the structural basis for different types of RHIM amyloid assembly associated with necroptosis in response to insult and under pathological conditions, such as neurodegeneration, ischemia and microbial infection.
The formation of stable, fibrillar protein assemblies is associated with many disease states, including Alzheimer's disease and Type II diabetes. These are non-functional deposits. Protein aggregates that have similar structural features but which are functional have been identified in several microorganisms. In these cases the self-assembly of the protein is advantageous to the organism. For example, hydrophobins are fungal proteins that self-assemble in an ordered manner into amphipathic films at air:water interfaces. They reduce the surface tension at air:water boundaries and form very hydrophobic coatings on fungal spore surfaces which facilitate dispersal in air. Hydrophobin assemblies share the ordered beta-sheet structural core that has been characterized in amyloid deposits.
Hydrophobin assemblies shield the human pathogenic fungus Aspergillus fumigatus from the immune response during infection, allowing this fungus to go on to cause life-threatening invasive aspergillosis. In rice blast, the most important fungal disease of rice, infection of the plants is facilitated by the production of a hydrophobin layer by the fungus Magnaporthe grisea. We are therefore interested in studying the biophysical and structural basis for the self-assembly of hydrophobins, with a view to understanding the role played by these proteins in fungal infections. Hydrophobin monolayer formation is a unique system that combines protein self-assembly with the generation of functional surfaces. These remarkable properties suggest a range of commercial applications, including biocompatibility enhancement of medical implants and emulsion and dispersion applications in foods and pharmaceuticals. This project involves using mutagenesis to probe the effect of sequence on hydrophobin structure and the study of the self-assembly process with techniques such as fluorescence, nuclear magnetic resonance, X-ray fibre diffraction and electron microscopy. Our work aims to develop a detailed picture of hydrophobin organisation within surface films. We hope to manipulate the self-assembly properties of the hydrophobins for the rational design of novel biological polymers and to design molecules that inhibit fungal spore dispersal and colonisation.
We have recently discovered that certain viral proteins can inhibit the host programmed cell death pathway necroptosis. This occurs by formation of heteromeric amyloids fibrils composed of both viral and host proteins that contain the amyloidogenic sequences known as RHIMs (RIP Homotypic Interaction Motifs). The Sunde group has applied single molecule methods to characterise these hetero-amyloids and to reveal this novel viral sequestration of host proteins and the molecular basis for viral inhibition of RHIM-based signalling in mammalian cells. This project aims to investigate the structural basis for different types of RHIM amyloid assembly associated with necroptosis in response to insult and under pathological conditions, such as neurodegeneration, ischemia and microbial infection.
研究兴趣
论文共 112 篇作者统计合作学者相似作者
按年份排序按引用量排序主题筛选期刊级别筛选合作者筛选合作机构筛选
时间
引用量
主题
期刊级别
合作者
合作机构
Natalie Trinh, Kaustubh R. Bhuskute, Nikhil R. Varghese, Jessica A. Buchanan, Yijia Xu,Fiona M. Mccutcheon,Robert L. Medcalf,Katrina A. Jolliffe,Margaret Sunde,Elizabeth J. New,Amandeep Kaur
bioRxiv (Cold Spring Harbor Laboratory) (2023)
Manjeet Kumar,Sarah L. Teakel,Crystall Swarbrick, Intifar S. Chowdhury,David C. Thorn,Margaret Sunde,John A. Carver,Jade K. Forwood
FEBS JOURNALno. 16 (2023): 4057-4073
Rezwan Siddiquee,Victor Lo, Caitlin L. Johnston,Aston W. Buffier,Sarah R. Ball, Jonathan L. Ciofani, Yi Cheng Zeng,Mahiar Mahjoub,Wojciech Chrzanowski,Shahrzad Rezvani-Baboli,Louise Brown,Chi L. L. Pham,
Biomacromoleculesno. 11 (2023): 4783-4797
BIOMACROMOLECULESno. 1 (2023): 5-23
SCIENCE ADVANCESno. 46 (2023)
加载更多
作者统计
合作学者
合作机构
D-Core
- 合作者
- 学生
- 导师
数据免责声明
页面数据均来自互联网公开来源、合作出版商和通过AI技术自动分析结果,我们不对页面数据的有效性、准确性、正确性、可靠性、完整性和及时性做出任何承诺和保证。若有疑问,可以通过电子邮件方式联系我们:report@aminer.cn