Protein conformational diseases with pathological consequences such as those leading to neurodegeneration and dementia, coincide with the formation and accumulation of protein aggregates in affected cells/tissues over time leading to cellular proteostasis breakdown. Often, symptoms linked to these disease conditions become apparent only in the long-lived, aging communities and thus, largely limits our ability to develop preventive therapeutics.

The Nillegoda group is probing attractive new proteostasis-based directions for future therapeutic interventions that could potentially slow and/or reverse neurodegeneration and are applicable for a broad range of disorders from Alzheimer’s disease to Multiple sclerosis.



Aggregation of cellular proteins is amplified upon exposure to various acute proteotoxic stresses (e.g. oxidative damage; heat shock), chronic disease conditions (e.g. neurodegeneration) and aging. The Nillegoda group utilises cutting-edge in vitro and in vivo techniques to study chaperone-based protein quality control machineries mediating protein aggregate solubilization and clearance, a process central to restoring and linked to organismal fitness. A major focus of the group is to study the regulation of human protein disaggregases (aggregate solubilization machines) under physiological and pathophysiological conditions. These studies provide insights onto the molecular basis of onset and progression of neurodegenerative diseases, and allow us to device strategies to boost aggregate clearance in affected tissues to reduce associated neurotoxicities.

Open positions in the Nillegoda Group

Domestic PhD students

Investigating the role of the Hsp70 chaperone system in neurodegeneration and immunity

We are currently looking for outstanding prospective PhD students for two exciting projects. Candidates must have an H1 Honours degree (or equivalent) or Masters degree in cell biology, biochemistry, biomedical sciences, immunology, neuroscience, or in a closely related field. Interested students are encouraged to send their CV and academic transcripts to Nadinath Nillegoda at

For more information: 

Mechanism of amyloid induced neuroinflammation in Alzheimer’s disease and Parkinson’s disease

This is a funded position, part of the collaboration between Monash and the Chinese University of Hong Kong. The student will spend at least 4 months at CUHK. Contact Nadinath Nillegoda at for more information.

For more information: 

Honours/Masters Students

A motivated student is sought for an Honours/Masters project focused on studying the regulation of human protein disaggregases (aggregate solubilization machines) under physiological and pathophysiological conditions. Contact  Nadinath Nillegoda at for more information.

Postdoctoral Fellows

Postdoctoral candidates with solid publication track records and keen in joining the laboratory are invited to contact at in order to discuss the application.

Nillegoda Group members
  • Characterizing the poorly understood role of protein disaggregases in protein conformational diseases in humans
  • Dissecting novel regulators of protein disaggregation
  • Exploring the J-domain protein (Hsp40)-Hsp70 chaperone networks vital for aggregate clearance in human cells
  • Developing methods for capturing molecular dynamics of distinct Hsp70 chaperone machineries in vivo


Featured Publications

More Publications

Published In

Kampinga HH, Andreasson C, Barducci A, Cheetham ME, Cyr D, Emanuelsson C, Genevaux P, Gestwicki JE, Goloubinoff P, Huerta-Cepas J, Kirstein J, Liberek K, Mayer MP, Nagata K, Nillegoda NB, Pulido P, Ramos C, De Los Rios P, Rospert S, Rosenzweig R, Sahi C, Taipale M, Tomiczek B, Ushioda R, Young JC, Zimmermann R, Zylicz A, Zylicz M, Craig EA, Marszalek J.

Function, evolution, and structure of J-domain proteins.

Garcia VM, Nillegoda NB, Bukau B, Morano KA.

Substrate binding by the yeast Hsp110 nucleotide exchange factor and molecular chaperone Sse1 is not obligate for its biological activities.

Mol Biol Cell. 2017 Jul 15;28(15):2066-2075. doi: 10.1091/mbc.E17-01-0070. Epub 2017 May 24.

Żwirowski S, Kłosowska A, Obuchowski I, Nillegoda NB, Piróg A, Ziętkiewicz S, Bukau B, Mogk A, Liberek K.

Hsp70 displaces small heat shock proteins from aggregates to initiate protein refolding.

EMBO J. 2017 Mar 15;36(6):783-796. doi: 10.15252/embj.201593378. Epub 2017 Feb 20.

Hsieh TY, Nillegoda NB, Tyedmers J, Bukau B, Mogk A, Kramer G.

Monitoring protein misfolding by site-specific labeling of proteins in vivo.

PLoS One. 2014 Jun 10;9(6):e99395. doi: 10.1371/journal.pone.0099395. eCollection 2014.

Theodoraki MA, Nillegoda NB, Saini J, Caplan AJ.

A network of ubiquitin ligases is important for the dynamics of misfolded protein aggregates in yeast.

J Biol Chem. 2012 Jul 6;287(28):23911-22. doi: 10.1074/jbc.M112.341164. Epub 2012 May 16.

Mandal AK, Theodoraki MA, Nillegoda NB, Caplan AJ.

Role of molecular chaperones in biogenesis of the protein kinome.

Methods Mol Biol. 2011;787:75-81. doi: 10.1007/978-1-61779-295-3_6.

Nillegoda NB, Theodoraki MA, Mandal AK, Mayo KJ, Ren HY, Sultana R, Wu K, Johnson J, Cyr DM, Caplan AJ.

Ubr1 and Ubr2 function in a quality control pathway for degradation of unfolded cytosolic proteins.

Mol Biol Cell. 2010 Jul 1;21(13):2102-16. doi: 10.1091/mbc.e10-02-0098. Epub 2010 May 12.

Mandal AK, Gibney PA, Nillegoda NB, Theodoraki MA, Caplan AJ, Morano KA.

Hsp110 chaperones control client fate determination in the hsp70-Hsp90 chaperone system.

Mol Biol Cell. 2010 May 1;21(9):1439-48. doi: 10.1091/mbc.e09-09-0779. Epub 2010 Mar 17.

Mandal AK, Nillegoda NB, Chen JA, Caplan AJ.

Ydj1 protects nascent protein kinases from degradation and controls the rate of their maturation.

Mol Cell Biol. 2008 Jul;28(13):4434-44. doi: 10.1128/MCB.00543-08. Epub 2008 Apr 28.

Jones J, Wu K, Yang Y, Guerrero C, Nillegoda NB, Pan ZQ, Huang L.

A targeted proteomic analysis of the ubiquitin-like modifier nedd8 and associated proteins.

J Proteome Res. 2008 Mar;7(3):1274-87. doi: 10.1021/pr700749v. Epub 2008 Feb 5.

Cdc37 has distinct roles in protein kinase quality control that protect nascent chains from degradation and promote posttranslational maturation.

J Cell Biol. 2007 Jan 29;176(3):319-28. doi: 10.1083/jcb.200604106. Epub 2007 Jan 22.