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For many neurodegenerative disorders, it is well known that clusters – or aggregates – of certain proteins accumulate in neurons and are contributors to disease. However, we still don’t know what causes these aggregates to begin forming inside the cells and how they contribute to disease development. Soumik Ray is establishing an independent research group which will study exactly this.

Cells are busy, complex entities, with areas which contain high concentrations of these proteins. Over time, the proteins can spontaneously assemble into larger structures, even in healthy tissue. Under normal circumstances, this assembly process is matched by a corresponding disassembly, creating a steady state; and it’s the periodic cycling of such assembly-disassembly processes, which Soumik Ray and his team are endeavouring to better understand in the context of neurodegeneration.

“Protein aggregates in neurodegenerative diseases are well understood but we don’t know how they begin forming, or how they suddenly appear.”

Until now, researchers have looked at individual components of this complicated protein landscape, but according to Soumik Ray, we need to factor the full complexity of these processes into our thinking, in order to know how the different components are influencing each other and how this contributes to the development of diseases like Parkinson’s, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia.

“When this periodic cycling is ongoing, there will eventually come a time where a combination of different assembly states co-exist, and these can influence each other. We don’t know anything about the co-existence of assembly states, but these must be considered in concert with each other, throughout the progression of disease.”

Soumik Ray has developed methodologies to screen libraries of different assembly states at high throughput, to study the aggregate landscape of any biomolecule. Together with a better fundamental understanding of this system, Soumik Ray is also optimistic about developing a diagnostic device to detect these aggregates in an earlier stage of disease than is feasible today. 

“What we have been doing for the last 50 years is a lot of quantitative biophysics - gather data, build revised models, fit the data, and extrapolate findings – but now my work has proved that the existing models are too simple, so we would need revised models to account for the cycling framework. That’s the central aim of this project.”

With better insight into the periodic cycling of assembly-disassembly processes in healthy and diseased conditions, Soumik Ray aims to identify drug targets within the cell that can aid the development of medical interventions for the ultimate benefit of the millions of people suffering from neurological disorders. 

Having completed his studies in India, Soumik Ray is enthusiastic about now becoming established as an independent researcher in Denmark:

“Building these new models is really exciting and brand new. If someone from a warm country can be convinced to go to work on a snowy Tuesday in Denmark, then it really must be exciting,” he says.