Unraveling the causes of Parkinson’s disease

1. Tell us a few things about your family, was it a typical Greek family?

 I grew up in Athens and my parents come from two different Greek islands but spent most of their lives in Athens. We lived like most Greek families.

2. Where did your parents come from and what is your connection with your roots?

My mother comes from Kerkyra (Corfu) and my father comes from the island of Symi in Dodekanisa. I am really connected to both of these places. I spent most of my summers in either of the two islands. Obviously I have relatives in both of them and I never lost contact with them. These are islands very different with respect to each other, with different topography, climate, natural resources and traditions. I feel at home in both of them.

3. Do you have any special memories from your childhood?

Yes, I have a wide range of memories dating back in my childhood in Greece. One such example which I could perhaps describe here is during the trips by boat to the Dodekanisa islands with my family. In those trips we used to spend most of the time outside, on the deck. My brother and I had many discussions then and I was thinking a lot about what I would like doing or ‘’becoming when I would grow up’’.

4. Your mother is a doctor, your father is an Astrophysics Professor in the University of Athens and your brother is a neuroscience researcher in MIT Boston. You didn’t fall far from the tree as we say. How did you choose your field of expertise?

I was always interested in physics, or in general in the natural sciences. Obviously, my family provided me with strong influences and I was lucky to get a lot of input from them, in particular in physics by my father and my brother. Later on, through my mother, I developed a strong interest in actual ways of using physics and engineering in order to develop new methodologies that can contribute to the understanding of pathogenic conditions that cause a lot of human suffering. And furthermore in how we can apply such new techniques for the development of novel diagnostic and therapeutic strategies. I therefore have been trying to link my background in electrical engineering and physics to the new emerging field of biophysics. It is with the combination of different disciplines and expertises that we can understand the complexity of phenomena that take place in a biological context.

5. What are your main research targets this period?

I have now a new position at ETH Zurich – it is the university where I did my PhD. In my new position I am developing the methodologies and techniques I developed in Cambridge (the super-resolution microscopy techniques) with a focus, on one hand, on the continuation of the study of Parkinson’s disease, but also I will extend this to other pathogenic conditions that are linked to function/dysfunction of proteins. Proteins are fundamental building blocks of living matter but they can undergo certain complex processes which are not yet fully understood.

6. Recently we learned that your team may be closer to unraveling the underlying causes of Parkinson’s disease, after identifying the point at which alpha-synuclein – a protein believed to play a key role in the condition – becomes toxic to the brain. Can you tell us a few things about your research?

In this work we developed and applied the so called super-resolution microscopy techniques (the inventors of which got the Nobel Prize in Chemistry in 2014) and we were able to visualize directly ‘’what was happening’’ in neuronal cell cultures (dissected from embryonic rat brain) monitoring the protein alpha-synuclein. The method we used not only is non-invasive (compared for example to Electron microscopy) and offers nanometer resolution, but also it has high sensitivity so we could monitor processes that happen at the very low physiological concentrations.

Parkinson’s disease is a neurodegenerative disease linked to the phenomenon which occurs when the naturally present in neurons protein alpha-synuclein folds into the wrong shape and then self-assembles eventually forming thin filament-like structures, highly ordered, called amyloid fibrils. The deposits of aggregated alpha-synuclein amyloid fibrils, also known as Lewy bodies, are the hallmark of Parkinson’s disease. Two of the most acute questions are: how does this assembly of the amyloid fibrils happen in neurons and what causes the toxic effect to neurons, or when do neurons die, in other words.

One of the important findings of this work was that the soluble form of alpha-synuclein, exogenously added, didn’t interact with the endogenous alpha synuclein protein that was already present in the neuron and interestingly this was where we saw toxic effects. This showed to us that the damage appears to be done before higher order fibrils are formed.
On the contrary, when adding preformed alpha-synuclein fibrils to the neurons, these ‘’consumed’’ the endogenous alpha-synuclein protein (that was already in the neuronal cell) and no toxic effects were present. Finally, by adding the soluble form of alpha-synuclein together with the preformed fibrils, we were able to counteract the toxic effect of the former. It appeared that the amyloid fibrils acted like ‘’magnets’’ for the soluble protein and ‘’absorbed’’ the soluble protein pool, shielding against the associated toxic effects.

Using therefore such optical super-resolution techniques, we can really visualize processes and ‘’see’’ details we couldn’t see before, and therefore proceed a step further into the understanding of the complex mechanisms that govern such diseases.

7. Do you believe that a cure for Parkinson’s disease will be probable in the future?

I am very optimistic about the future: there is an increasing momentum in combining disciplines, expertises and methodologies from different scientific fields that work together to tackle the disease from different angles. There has been a lot of progress in the last years and I also think key to this will be the possibility for an early diagnosis and the understanding of which processes should be addressed directly.

8. Would you consider returning to Greece in the future? And if so under which circumstances?

I miss Greece and I would consider seriously to come back – I would like though to be able to fulfill a role in which I could contribute to the scientific or educational landscape.

9. What is your motto in life?

Learn from any difficult situation or problem, become a better person and keep up the optimism and the perseverance.

10. How often do you visit Greece?

Typically 3 times per year.

11. What does Greece mean for you?

Greece is my home, my roots and the place where I acquired the most important memories, the foundation of my education and the triggering of my scientific aspirations.


Unraveling the causes of Parkinson’s disease

Dorothea Pinotsi is a post doc researcher in the Department of Chemical Engineering and Biology in Cambridge University.

Her research focuses on the development of new techniques that allow us to depict the biological nanostructures in real time, mostly regarding the neurodegeneration of the brain.

Her mother is a doctor, her father is an Astrophysics Professor in the University of Athens and her brother is a neuroscience researcher in MIT Boston.

She graduated fron the department of Electrical Engineering (National Technical School of Athens) in 2006, and got her PhD in Quantum Photonics in 2011 from the Swiss Federal Institute of Technology in Zurich (ETH).

In 2012 she got a scholarship from the Swiss National Science Foundation (SNF) that gave her the chance to be the part of a scientific team in Cambridge that studied neurodegenerative diseases, such as Parkinson’s and Alzheimer’s, through the developoment of new techniques in optical microscopy.

“Such findings change the way we look at the disease, because the damage to the neuron can happen when there is simply extra soluble protein present in the cell – it’s the excess amount of this protein that appears to cause the toxic effects that lead to the death of brain cells.”

Along with her team in March 2016, she was able to observe for the first time the exact moment in which proteins associated with Parkinson’s disease become toxic to brain cells. Researchers have used a non-invasive method of observing how the process leading to Parkinson’s disease takes place at the nanoscale, and identified the point in the process at which proteins in the brain become toxic, eventually leading to the death of brain cells. The results suggest that the same protein -alpha-synuclein- can either cause, or protect against, the toxic effects that lead to the death of brain cells, depending on the specific structural form it takes.


  Comments: 6

  1. Σπυρος Λυκοπουλος

    Μακαρι να βλεπουμε ολο και πιο πολλους Ελληνες να διαπρεπουν. !!!
    Να χαμογελας παντα. !!!!

  2. Δημήτρης Σταυρόπουλος

    Μας κάνει περήφανους, Εύγε της Της εύχομαι καλή συνέχεια.

  3. Δημήτρης Σταυρόπουλος

    Άξια συγχαρητηρίων και όχι μόνο. Εύγε της. Της εύχομαι να έχει καλή συνέχεια.

  4. Ελενη Μηναδακη – Μιχαηλιδου

    Θερμοτατα συγχαρητηρια! Ειμαι περηφανη για σενα Δωροθεα!Ησουν γνωστη με τον συζυγο μου. Εργαζοταν στου Παπασωτηριου.Ευχομαι απο καρδιας κ εις ανωτερα! Το αξιζεις. Πνοη ζωης για χιλιαδες πασχοντες…Φιλακια πολλα!



  6. Αναστασία Πάπα

    …η ΕΛΠΙΔΑ της Ανθρωποτητας!!! Ενα τεραστιο ΜΠΡΑΒΟ για τον Αγωνα σου!!! ΙΣΤΙΑΙΑ ΕΥΒΟΙΑΣ, 04/03/2017