Cell exploration paving the way for new breakthroughs

LIFE’s elite research area for bioimaging

Bioimaging is advanced supermicroscopy which makes it possible for researchers in LIFE’s elite research area to look into living cells.

By monitoring developments in both healthy and diseased cells, researchers are gaining completely new knowledge about as yet unknown cell functions and properties.

 

The method is opening up new possibilities for making great strides with research into stem cells, cancers, diabetes, food quality, synthesis biology, animal reproduction and plant biotechnology.

 

By Katherina Killander

 

 

We asked the anchorman for LIFE’s elite research area in bioimaging, Professor Alexander Schulz, eight key questions about the elite research area:

• Where is bioimaging currently heading as a field?
• How is LIFE contributing to bioimaging research worldwide?
• Which promising research projects would you otherwise like to mention?
• If the elite research area becomes the projected success in the coming years, what do you hope to achieve?
• How will LIFE students benefit from the elite research area?
• What are your considerations in relation to collaborating with stakeholders such as companies, authorities or others that may have a particular interest in this specific elite research area?
• Where can you follow the elite research area’s results?
• Who is behind the elite research area?

Where is bioimaging currently heading as a field?

 

Professor Alexander Schulz replies:

“Bioimaging is a relatively new field which has existed for about 15 years. In 2008, the Nobel Prize was actually awarded to a group of researchers who laid one of the most important foundation stones for the field’s subsequent success:  They extracted the green fluorescent protein (GFP) out of jellyfish and modified it, so it could be introduced into all living cells, both animal cells, plant cells, fungal cells and bacteria. (see http://nobelprize.org/nobel_prizes/chemistry/laureates/2008/tsien-lecture.html)

 

 

Like men from space

The fluorescent protein and its function can be illustrated in the following way:

Imagine a group of men from space sitting on a roof. They have drilled a hole through the roofing which gives them unrestricted views of a classical music concert taking place in the hall beneath them. Violinists, wind instrumentalists and other musicians are in full swing. The men from Mars have no idea what’s happening because they have never heard music before, experienced a concert or held a musical instrument in their hands.

To find out what is happening, they place a fluorescent lamp on one of the violinist’s feet. The lamp lights up as the violinist makes his way to his chair, and the Martians observe what he does. Slowly, the Martians start to get an impression of what is happening.

 

Depending on where they place the lamp, they learn different things. The fluorescent protein we use in bioimaging can be illustrated by the Martians’ lamps, which light up and create new knowledge about unknown elements in the cell.

 

 

Life’s networks revealed yet undisturbed

In bioimaging, we are trying to look into living cells without disturbing them. This enables us to get as close to reality as possible.

 

We want to see how life’s networks freely unfold in the cell, so we place ‘lamps’ in different places. Usually the fluorescent protein, which is available today in all the colours of the rainbow, is inserted into the cell’s nanomachinery i.e. the proteins.

 

The proteins perform mechanical work such as the cell’s movements, enzymatic work which produces chemical reactions that cannot happen spontaneously, and transportation work which transfers metabolites from one part of the cell to another, and from one cell to a neighbouring cell. The cell’s signalling and coordination with other cells also involve specialist proteins.

Video recordings inside the cell

Back in the 1960s, it was only possible to produce still images of the cell, for example with transmission electron microscopy. However, because it was first necessary to kill the cell, the observation material was artificial. Now developments are so advanced that we can produce ‘video’ – in other words, live pictures of living cells.

 

Unlike the usual methods in molecular biology, with bioimaging we are able to look at several factors simultaneously, for example both the ‘conductor’ and the ‘violinist’ LIVE while they are working.

 

Another way of obtaining new knowledge about unknown cell functions is to knock a gene out to determine its function. As if the Martians bumped off the conductor. How would the music sound then?

 

You can also elect to copy a gene (‘copy the conductor’), i.e. overexpress the gene to see what happens.”

 

How is LIFE contributing to bioimaging research worldwide?

“As the first in Denmark, we will soon be getting a supermicroscope which can resolve the finest cell details.

 

It will further improve our possibilities for learning more about how the biology hangs together and about cell life. This super-resolution microscope is special because it enables us to resolve elements in the cell at a distance of less than 100 nanometres. By comparison, an ordinary light microscope can only resolve elements in the cell down to 300 nanometres.

 

Useful platform for international research

LIFE’s research area within bioimaging is making an international contribution that spans a wide range of research areas because it is such a useful platform. From stem cell research, animal reproduction, diabetes research and food quality to synthesis biology and cell communication in plants. In the past few years, more than 90 research groups have taken advantage of LIFE’s facilities.

Bioimaging ensures successful grafting that benefits agriculture

Grafting is a concrete example of how applicable bioimaging is. In agriculture, many vegetables and fruit are grafted, for example cucumbers and apples. They are grafted onto a robust rootstock such as pumpkin or quince, respectively, as these are very resistant to parasites and pests.

 

Good cell communication vital for grafting

Successful grafting requires the involvement of several factors. First, the two crops must grow well together, water from the roots must be taken up by the scion, and finally, the cells in, for example, the apple and the quince need to ‘talk’ well together. Some vegetables will never be suitable for grafting as they are unable to communicate with each other.

 

Previously, it has been not been possible to predict this cell communication, and it has therefore been more or less haphazard as to whether the grafting will succeed. Often, the scion has failed to graft, with the branch falling off etc.

 

Bioimaging predicts in advance whether grafting is successful

However, thanks to a groundbreaking research project at LIFE, using bioimaging a method has been found for predicting whether grafting can succeed. This discovery has already been a huge benefit for agriculture.

 

Today, bioimaging is a key tool which is used in a wide range of research projects both at LIFE and elsewhere where researchers are seeking to understand the connection between the processes taking place inside the cells.”

 

Which promising research projects would you otherwise like to mention?

“We have started a project with the Technical University of Denmark (DTU) and the University of Southern Denmark (SDU) on the development of nanosensors in different cell types. The nanosensors tell us how things look inside the cell.  

 

To return to our illustration, you could say that instead of just placing a green lamp on the violinist, you can use nanosensors to indicate whether or not he is in a good mood by means of the colour changing from green to red.

 

Nanoscensors reveal cell stress

The nanosensors make it possible to measure the concentration of various substances in the cell and also whether the cell is stressed. This is only feasible thanks to bioimaging, which is capable of observing the state of the cells. The nanosensors can be used, for example, to see whether a particular fertiliser stresses the plant and which fertilisers enhance its growth.

 

We also use nanosensors to measure pH values in growing roots so we can follow their growth direction. It is fascinating to see what happens when a plant’s roots hit a stone. What happens – and where does the plant choose to push its roots?

 

Research driven by fascination and curiosity

Our research with bioimaging is naturally driven by a desire for progress within lots of research areas, but also by our curiosity about and fascination for everything we don’t yet understand.

A plant is like a society of cells which are all equipped with the same genomic code, the same ‘book’. Nevertheless, they are carefully organised in working groups which, with great precision, are working for the larger community. Some cells issue commands to others when the situation demands it. And the tasks are always solved – however, not always without discussion. We still don’t know whether similar cell communication is found in animals.

 

The cell society – the ideal society

In my view, the cell society represents an ideal where everyone is equal. Some cells are even prepared to sacrifice themselves for the greater good – by committing suicide, for example, to make space for water transport.

 

Tasty cheese with bioimaging

Within food research, we use bioimaging to develop cheeses with special consistencies and properties, for example low-fat cheese with improved consistency and taste.

New bioimaging centre attracting researchers from around the world

The bioimaging research was further strengthened following the inauguration of the University of Copenhagen’s new Center for Advanced Bioimaging (CAB) on 23 June, where the faculties LIFE, SCIENCE and FARMA are working together. In addition to the best measuring equipment in the country, we also expect the centre to attract some of the best researchers and students from Denmark and abroad.”

 

If the elite research area becomes the projected success in the coming years, what do you hope to achieve?

“We want to make the most of the coming super-resolution microscope and other microscopes which are on the way to generate more knowledge about cells’ reciprocal communication.

Another success criterion is that a large number of people use our equipment in the new bioimaging centre, for example researchers from Denmark and abroad who we can train to solve tasks on their own with it.

Moreover, in future we will give businesses the opportunity to carry out their trials here.

 

Well known among businesses and researchers throughout Denmark

It is wonderful that Danish researchers do not have to travel abroad but can instead use our facilities. Boasting three confocal microscopes, many businesses and researchers already know of our facilities.

 

Another sign of success will be that our PhD students and postdocs acquire even stronger competencies within the new bioimaging methods, giving them a valuable supplement to their microbiological competencies.”

How will LIFE students benefit from the elite research area?

“It will give them better educational opportunities. For example, they will have access to some of the best equipment in the world and also learn in detail how to use supermicroscopes.”

 

What are your considerations in relation to collaborating with stakeholders such as companies, authorities or others that may have a particular interest in this specific elite research area?

“As mentioned, we are already working with numerous businesses and research institutions throughout Europe, but what we really want is funding to develop a new X-ray detector with extremely high penetration. This will allow us to see even further into plants and animals.”

Where can you follow the elite research area’s results?

“In conjunction with CAB’s inauguration, we will launch a portal with regular news updates. Until then, you can follow developments via the LIFE website and in international periodicals.”

 

Who is behind the elite research area?

“Myself and Lars-Inge Larsson, as well as research groups headed by the following: Birger Lindberg Møller, Richard Ipsen, Dan Holmberg, Poul Huttel and Michael Palmgren.”