Dr Nadinath Nillegoda is a molecular and cell biologist studying cellular repair mechanisms that help maintain protein homeostasis (proteostasis). Nadinath received his PhD in Biomedical Sciences from the Mount Sinai School of Medicine of New York University (New York, USA), where he identified a novel cellular protein quality control pathway that degrades aberrant or misfolded proteins thus filling an essential knowledge gap in eukaryotic proteostasis. He then joined the Group of Prof. Bernd Bukau at the Center for Molecular Biology, Heidelberg University (Heidelberg, Germany) as an Alexander von Humboldt Postdoctoral Fellow. In Heidelberg, Nadinath published his seminal work on the human Hsp70 chaperone-based protein disaggregases that are fundamentally important for protein aggregate clearance during cell repair in multicellular organisms. His reports are the first to describe the (patho)physiological impact of this activity in organismal health, disease, and aging. During his brief Project Leadership at the German Cancer Research Centre (DKFZ) and Center for Molecular Biology (Heidelberg), Nadinath provided the first evolutionary insight into the emergence of Hsp70-based protein disaggregation function.

In Nov. of 2018, Nadinath was appointed as a Group Leader at the Australian Regenerative Medicine Institute at Monash University in Melbourne, Australia, to explore the potential therapeutic gain of boosting protein disaggregation activity that will lead to new treatments for disorders associated with neurodegeneration. Neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD) are often characterized by the formation and persistence of protein aggregates (amyloids) in neuronal tissue that initiate the disease process by a gain-of-toxicity mechanism. The cellular surveillance systems that usually keep proteins in check deteriorate during aging and become overwhelmed in such chronic disease conditions, thus leading to increased protein misfolding/aggregation. Such a collapse in proteostasis ultimately triggers apoptosis of the affected neurons and drives neurodegeneration. Nadinath’s research opens the possibility to reverse, rather than prevent aggregation, therefore, is an attractive new direction for future therapeutic interventions for neurodegenerative diseases and a broad range of other protein conformational disorders (e.g. Type II diabetes) that have limited or no cures.

The Nillegoda laboratory started operating in April 2019 and is currently looking for talented and highly motivated students (H1 honours, MSc and PhD levels) and budding Postdoctoral Fellows to study key regulatory mechanisms of protein disaggregation vital for facilitating neuronal repair in AD and PD. The Group is also investigating the interplay between neurodegeneration and immunity with a focus on multiple sclerosis.

Using rodent models to understand the (patho)physiological impact of protein aggregate solubilization (disaggregation) in neurodegenerative (Alzheimer's disease and Parkinson's disease) and metabolic (Type II diabetes) diseases in humans

Exploring the interplay between neurodegeneration and immunity

Dissecting novel regulators of the human Hsp70-based protein disaggregases

Developing proximity-based methods for capturing dynamic protein-protein interactions in human cells using high sensitive fluorescence microscopy