Research Fellow trying to understand how cells keep their proteins healthy. Python enthusiast and passionate believer in coding for life scientists.
Biography
Dr Dezerae Cox is a Research Fellow working to uncover the fundamental drivers Motor Neuron Disease. Her work focuses on the application of novel single-molecule super-resolution microscopy and proteomics methods to characterise protein aggregates from disease-derived tissues and biofluids. Dezerae completed her PhD on small heat shock molecular chaperones in 2016 at the University of Wollongong, before joining the University of Melbourne in 2017 where she developed novel proteomics-based biosensors of proteostasis in live cells. Dezerae moved to the University of Cambridge in 2021 as a Lady Edith Wolfson Junior Non-Clinical Research Fellow supported by the Motor Neurone Disease Association.
As a self-taught computer programming enthusiast, Dezerae is a passionate advocate for the use of programming by life scientists. She routinely uses Python scripting for day-to-day data analysis, and hosts regular Hacky Hours for biologists new to the world of big data science. By encouraging and mentoring fellow early-career scientists to develop these skills, she hopes to show them how integrating programming skills into their research can empower them to seek out and solve more profound problems than ever before.
Research
Dezerae is currently a Research Fellow at the University of Cambridge, UK, where she works with Professor Sir David Klenerman’s lab to uncover the fundamental drivers of neurodegenerative disease. These diseases, including Alzheimer’s (AD), Parkinson’s (PD) and Motor Neuron (MND/ALS) disease, are unified by a failure in the machinery that normally keeps our cells healthy – the proteostasis network. Failures in this network allow the accumulation of damaged protein molecules into clumps within the brain.
Despite decades of research, we do not yet have a straight answer as to the role of these clumps in disease onset and progression. Protein clumps, or aggregates, are rare and often heterogeneous, making them an elusive target for researchers trying to understand, prevent or reverse their toxicity. Dezerae is devising sensitive microscopy methods to fingerprint protein aggregates released from the brains of MND patients. She hopes to then produce a matching fingerprint from model systems routinely used in laboratory research. The matching model will allow researchers around the globe to interrogate aggregate properties associated with disease, opening the door to new treatments that specifically target these toxic properties. Such a discovery has the potential to impact a broad international community across the spectrum of neurodegenerative diseases to drive new diagnostic, preventative and therapeutic measures.
Publications
ψ Cox, D., Ang, C., Nillegoda, N. B., Reid, G. E., and Hatters. D. M. (2021) Hidden Information on Protein Function in Censuses of Proteome Foldedness. Nature Communications, doi: 10.1038/s41467-022-29661-2.
Cox D, Ormsby AR, Reid GE, *Hatters DM (2022) Protein painting reveals pervasive remodeling of conserved proteostasis machinery in response to pharmacological stimuli. bioRxiv, doi: 10.1101/2022.05.14.491969 * Co-corresponding authors
Mathangasinghe Y, Alberts N, Rosado CJ, Cox D, Payne NL, Ormsby AR, Alp KM, Sakson R, Uthishtran S, Ruppert T, Arumugam S, Hatters DM, Kampinga HH, Nillegoda NB (2022) Cellular aging impedes stress-activation of a crucial JDP-Hsp70 protein disaggregase. bioRxiv doi: 10.1101/2022.06.25.497591
Carmo OMS, Shami GJ, Cox D, Liu B, Blanch AJ, Tiash S, Tilley L, Dixon MWA. (2022) Deletion of the Plasmodium falciparum exported protein PTP7 leads to Maurer’s clefts vesiculation, host cell remodeling defects, and loss of surface presentation of EMP1. PLoS Pathogens, doi: 10.1371/journal.ppat.1009882.
*Raeburn CB, *Ormsby AR, *Cox, D, Gerak CA, Makhoul C, Moily NS, Ebbinghaus S, Dickson A, McColl G, Hatters DM. (2022) A biosensor of protein foldedness identifies increased “holdase” activity of chaperones in the nucleus following increased cytosolic protein aggregation. Journal of Biological Chemistry, doi: 10.1016/j.jbc.2022.102158 *Equal contributions
Ruff KM, Choi YH, Cox D, Ormsby AR, Myung Y, Ascher DB, Radford SE, Pappu RV, Hatters DM. (2022) Sequence grammar underlying the unfolding and phase separation of globular proteins. Molecular Cell doi: 10.1016/j.molcel.2022.06.024.
Sui, X., Cox, D., Nie, S., Reid, G. E., & Hatters, D. M. (2022). A Census of Hsp70-Mediated Proteome Solubility Changes upon Recovery from Heat Stress. Journal of Proteome Research, doi: 10.1021/acs.jproteome.1c00920.
Sui, X., Radwan, M., Cox, D., & Hatters, D. M. (2022). Probing Protein Solubility Patterns with Proteomics for Insight into Network Dynamics. The Integrated Stress Response. Humana, New York, NY. doi: 10.1007/978-1-0716-1975-9_16
Whiten D.R., Cox D., Sue C.M. (2021) PINK1 signalling in neurodegenerative disease. Essays in Biochemistry. doi: 10.1042/EBC20210036.
Ormsby, A.R., Cox, D., Daly, J., Priest, D., Hinde, E., Hatters, D. M. (2020) Mutant Huntingtin exon 1 does not stall ribosomes during translation but does recruit machinery involved in ribosome quality control into inclusions. PlosOne. doi: 10.1371/journal.pone.0233583
Selig, E. E., Zlatic, C. O., Cox, D., Mok, Y. F., Gooley, P. R., Ecroyd, H., & Griffin, M. D. (2020). N-and C-terminal regions of αB-crystallin and Hsp27 mediate inhibition of amyloid nucleation, fibril binding, and fibril disaggregation. Journal of Biological Chemistry, doi: 10.1074/jbc.RA120.012748
San Gil, R., Cox, D., McAlary, L., Berg, T., Walker, A.K., Yerbury, J. J., Ooi, L., Ecroyd H. (2020) Neurodegenerative disease-associated protein aggregates are poor inducers of the heat shock response in neuronal-like cells. Journal of Cell Science doi: 10.1242/jcs.243709
Sui, X., Pires, D.E.V., Ormsby, A.R., Cox, D., Nie, S., Vecchi, G., Vendruscolo, M., Ascher, D.B., Reid, G.E., Hatters, D.M. (2020) Widespread remodeling of proteome solubility in response to different protein homeostasis stresses. Proc Natl Acad Sci U S A. doi: 10.1073/pnas.1912897117
Radwan, M., Ang, C., Ormsby, A. R. , Cox, D., Daly, J.C., Reid, G. E., Hatters, D. M. (2020) Arginine valency in C9ORF72 dipolypeptides mediates promiscuous proteome binding that stalls ribosomes, disable actin cytoskeleton assembly and impairs arginine methylation of endogenous proteins.Molecular & Cellular Proteomics doi: 10.1074/mcp.RA119.001888
Cox, D., Raeburn, C., Sui, X. & Hatters, D. M. (2018) Protein aggregation in cell biology: An aggregomics perspective of health and disease. Seminars in Cell & Developmental Biology. doi:10.1016/j.semcdb.2018.05.003
Whiten, D. R., Cox, D., Horrocks, M.H., Taylor, C.G., De, S., Flagmeier, P., Tosatto, L., Kumita, J.R., Ecroyd, H., Dobson, C.M., Klenerman, D., Wilson, M.R. (2018) Single-Molecule Characterization of the Interactions between Extracellular Chaperones and Toxic a-Synuclein Oligomers. Cell Reports 23, 3492–3500.
† Cox, D., Whiten, D.R., Brown, J., Horrocks, M.H., San Gil, R., Dobson, C.M., Klenerman, D., van Oijen, A.M., Ecroyd, H. (2018) The small heat shock protein Hsp27 binds α-synuclein fibrils, preventing elongation and cytotoxicity. Journal of Biological Chemistry, doi: 10.1074/jbc.M117.813865.
ψ Wood, R., Ormsby, A., Radwan, M., Cox, D., Sharma, A., Vöpel, T., Ebbinghaus, E., Oliveberg, M., Reid, G.E., Dickson, A., & Hatters, D.M. (2018) A biosensor-based framework to measure latent proteostasis capacity. Nature Communications 9: 287
Cox, D., & Ecroyd, H. (2017). The small heat shock proteins αB-crystallin (HSPB5) and Hsp27 (HSPB1) inhibit the intracellular aggregation of α-synuclein. Cell Stress and Chaperones, 22(4), 589-600.
ξ Cox, D., Selig, E., Griffin, M. D., Carver, J. A., & Ecroyd, H. (2016). Small Heat-shock proteins prevent α-synuclein aggregation via transient interactions and their efficacy is affected by the rate of aggregation. Journal of Biological Chemistry, 291(43), 22618-22629.
Cox, D., Carver, J. A., & Ecroyd, H. (2014). Preventing α-synuclein aggregation: the role of the small heat-shock molecular chaperone proteins. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1842(9), 1830-1843.
Hochberg, G. K., Ecroyd, H., Liu, C., Cox, D., Cascio, D., Sawaya, M. R., … & Robinson, C. V. (2014). The structured core domain of αB-crystallin can prevent amyloid fibrillation and associated toxicity. Proceedings of the National Academy of Sciences, 111(16), E1562-E1570.
₸ Recommended as an ACS Publication Editor’s Choice
† Recommended in F1000Prime as being of special significance in its field by F1000 Faculty Member Robert Petersen.
ψ Featured on the Nature Communications Editors’ Highlights Webpage as a particularly interesting or important new research article.
ξ Featured in Focus on Australasia. Journal of Biological Chemistry, Virtual Issue 2018 for outstanding contribution to Australian protein science.
Teaching and Supervisions
2023/2024:
- Introduction to Python - Trainer
2022/2023:
- Introduction to Python - Trainer
