Instant reaction: study of the midbrain

17 May 2017

Emmy Tsang (Croucher Scholarship 2016) is currently a predoctoral fellow of the Gross group, Mouse Biology Unit at the European Molecular Biology Laboratory in Italy. She began her PhD work in 2014, under the supervision of Dr Cornelius Gross and her PhD project looks at neuroscience and in particular how innate fear is processed in the brain. She focuses mainly on the periaqueductal gray (PAG, also known as the central gray) which is the primary control centre known to be important for regulating all the different types of instinctive behaviour, amongst other things.

Tsang grew up in Hong Kong where her father was a professor in mathematics and her mother a civil servant. She was always interested in science and after finishing her HKCEE she wanted to be exposed to overseas teaching methods and completed the final two years of her secondary education (6th form) at a private school in England.

“I always liked solving problems as a child- not only to find a solution but also to figure out different ways to approach problems,” she says and adds that she also enjoys trying to generalise things, in the sense of finding patterns and common rules that can explain seemingly random and unrelated objects. 

She studied chemistry and physics for her International Baccalaureate (IB), even though she was actually more interested in biology because she felt that physics and chemistry were more “fundamental” sciences.

“Without at least some sort of understanding in these areas, I would not be a very good biologist,” she says.

By the end of her third year in Cambridge, she knew she wanted to do a PhD but wasn’t sure in which field of science, so she decided to take the fourth-year system biology course, hoping to expose herself to bioinformatics, biostatistics and programming. These techniques were entirely new to her but ultimately became extremely useful in her PhD which was about neuroscience and also influenced her future research goals.

“Neuroscience appealed to me because the central nervous system is the most complex structure in a human body- and one that really separates us from other animals,” she says but she also thinks that big data is becoming increasingly important in biology in general and in neuroscience in particular.

“Studying individual cells generates huge amounts of data- for example, a photograph of a neuron may take 1MB, and there are 100 billion cells (neurons) in the human brain,” she says.

“Years of research have been invested in understanding how our brains work, but in my opinion, we haven’t even scratched the surface,” says Tsang. She remains fascinated by the fact that our nervous system, along with the rest of our body, stemmed from a single cell. In the process of our development, we went from being a single cell to a complex nervous system.

While she admits that the wonderful weather, food and culture made Italy an easy choice for her PhD studies, the Monterotondo outstation of the European Molecular Biology Laboratory appealed to her, professionally, because it’s a small institute with a diverse range of researchers. The Gross Lab’s particular interest is to draw the link between genes, molecules and behaviour and she says that Dr Cornelius Gross is a “great supervisor”.

“He gave me a blank cheque at the beginning of my PhD to pursue whatever question I wanted to, something I must stress is extremely uncommon,” she says.

Tsang explains that the most challenging aspect of her chosen field of expertise is the highly complex functions of the brain. She explains that the activity of brain cells depend on their molecular make up and this will vary between people based on the individual’s genes which are (in effect) instructions to make these molecules and they’re different between each subject.

“I am interested in finding the identity of the brain cells and one way of doing this is via gene expression- the instructions that make the cell work. If we can profile the molecules in that cell we have a good idea of what it does,” she says.

The laboratory she works in is primarily interested in understanding the neural circuits governing instinctive behaviour; that which is inborn and doesn’t require learning. Ethologists have classified them into three big groups: defence, reproduction and ingestion, which are all fundamental to any organism’s survival. 

Tsang is particularly interested in the periaqueductal gray (PAG) and her theory is that the cells in this area allow a subject to decide which instinctive cue to act towards. So, if you are starving and there’s some food near you, but the food is held by a bully who is going to beat you up, what would you do? To understand how all this works, she first needs to understand what types of PAG cells are important for each type of behaviour, and before that, she needs to know what types of cells there are in the PAG.

Fortunately, this is now more achievable using single cell RNA-sequencing which allows her to profile many many brain cells at the same time, so she can make a catalogue of all the different types of PAG cells. Then it is possible to start manipulating them and see what changes it makes to behaviour.

One behaviour she wants to understand in particular is social fear. 

In humans, this is more or less like fear towards a bully; we think this fear is inborn instinct. This is why her experiments are done with mice, as mice have basic social behaviours (fear, aggression, sex, etc.). By looking at the PAG brain cells in mice that govern social fear, she hopes ultimately that it will contribute towards an understanding of social fear in humans, and in the very long run towards related illnesses like post-traumatic stress disorder, depression and anxiety.

The award of a Croucher Scholarship enabled her to conduct her PhD research without worrying about the financial situation and what she found most helpful was the “academic development” subsidy, which allowed her to attend relevant conferences and courses.

Tsang realised during the course of her PhD work that she is possibly more interested in developing and optimising ways to solve problems than the questions and problems themselves. Post PhD she sees herself pursuing something related to neuroscience but perhaps being able to bridge the gap between pure biology and data science and information engineering.

More recently she has started programming and analysing big data intensively and finds herself constantly hooked onto data problems, algorithm development and machine learning.

“These are perhaps the most exciting and growing fields in this decade, and I’m eager to be part of it,” she says. 

Emmy obtained her masters and bachelor degrees in Natural Sciences from Churchill College, University of Cambridge. She began her PhD work in Italy in 2014, at the European Molecular Biology Laboratory Mouse Biology Unit, under the supervision of Dr. Cornelius Gross. Her PhD project looks at how innate fear is processed in the brain, focusing mainly on the periaqueductal grey, a midbrain structure known to be important for instinctive behaviours. Using a combination of mouse genetics, viral tracing and behavioural assaying techniques, she hopes to understand how the periaqueductal grey integrates information from upstream brain regions to produce the appropriate behavioural output. 

To view Emmy Tsang’s Croucher profile, please click here