Deciphering protein “barcodes”

28 May 2019

Biophysicist Dr Joyce Fung (Croucher Scholarship 2014) is delving into the intricate structures of proteins within biological systems to uncover fresh knowledge about protein structures and dynamics that can assist understanding related to diseases such as cancer and neurodegenerative disorders.

Fung is currently a postdoctoral researcher in the laboratory of Dr Elizabeth Rhoades at the University of Pennsylvania, where she is investigating intrinsically disordered proteins with no stable structure. In particular, she is interested in the tau protein, which is involved in several neurodegenerative conditions, including Alzheimer’s disease.

“Most studies focus on the pathology of tau, but we don’t know much about its normal function,” Fung noted. She is currently exploring how tau influences the stability and polymerisation of microtubules, which provide cells with structural support and intracellular transport.

Fung first moved to the United States from Hong Kong to pursue her undergraduate degree at Washington University in St Louis. She initially pursued biological research using mouse models, but later realised her interests lay at a more fundamental level.

Following graduation, Fung joined the University of Texas Southwestern Medical Center (UT Southwestern) to pursue a PhD in molecular biophysics. There, she was exposed to the world of structural biology and crystallography, a technique that enables scientists to visualise a protein’s shape in 3D.

During her graduate studies with Dr Yuh Min Chook, Fung focused primarily on a protein called chromosome region maintenance 1, or CRM1 for short. CRM1’s job is to ensure that various macromolecules inside a cell’s nucleus are exported to their destinations throughout the rest of the cell, facilitating the export of hundreds of different proteins from the nucleus.

“Each protein contains a sequence called a nuclear export signal, which is similar to a barcode,” Fung explained.

At the time, it was unknown how CRM1 could recognise so many different nuclear export signals. Fung and her co-authors were able to shed light on this mystery using crystallography, with the team successfully crystallising 13 different complexes between CRM1 and various nuclear export signals.

In a 2017 article in eLife, they published their discovery of two nuclear export signals that were bound to CRM1 in the opposite direction to that previously reported. Additionally, they found the structures of different signals to be surprisingly diverse, with only a single turn in the protein’s shape remaining consistent across all structures.

In a 2018 paper in Molecular Biology of the Cell, Fung took this research one step further by developing two small peptide inhibitors for CRM1. As many of CRM1’s cargo proteins are involved in tumour suppression and cell cycle regulation, mislocalisation of such cargoes can lead to cancer. This means Fung’s peptide inhibitors could be potentially useful within the field of cancer research.

Following the completion of her postdoctoral research at the University of Pennsylvania in June, Fung is planning to become an assistant instructor at her former laboratory at UT Southwestern, where she will apply her new experience with intrinsically disordered proteins and fluorescence-based methods to study nuclear pore proteins.



Dr Joyce Fung is a postdoctoral researcher at the University of Pennsylvania. Her research in the laboratory of Dr Elizabeth Rhoades centres on intrinsically disordered proteins involved in neurodegenerative diseases. She earned her A.B. in Biochemistry and Molecular Biology from Washington University in St Louis and a PhD in Molecular Biophysics from the University of Texas Southwestern Medical Center.


To view Dr Fung’s Croucher profile, please click here.