We are gradually learning more about the cells of the human body than any researcher has ever dared to dream of. But what’s the purpose?
The mere thought of what one plunges into when deciding to research cells is mind-blowing: The human body contains 37 trillion cells, plus/minus a few billion.
Despite the fact that they contain the same DNA, each cell behaves differently, depending on how they are affected by the body and each other.
As if this wasn’t enough, they can also switch between different stages, depending on the challenges they face.
That means a liver cell isn’t just a liver cell, and a skin cell isn’t just a skin cell. That’s the opposite of what researchers believed 50 years ago.
Back then, it was also estimated that there were around 200 different cell types, but increasingly advanced technology has allowed us to study the mechanisms in individual cells, and this has led to the discovery of many new cell types.
And new ones keep cropping up.
With that many different cell types, which can even switch between different stages, will we ever be able to fully comprehend how the human body works?
– Even though there are so many types of cells, and even though they interact differently, we have a good overview of the basic, general mechanisms for how, for example, a liver works.
– But it's like doing space research: We have an overview and qualified assumptions about what is out there – but we are also constantly discovering new planets and particles that lead to new knowledge and insight, says Kedar Natarajan.
He is an Assistant Professor and Head of Research at the Danish Institute of Advanced Science and the Department of Biochemistry and Molecular Biology.
His specialty is embryonic stem cells – which processes are in play when a fertilised egg begins to divide and give rise to all of the different cell types needed to build an organism?
He is also working on developing and improving techniques to find all of the currently undiscovered cell types and cell stages whose existence researchers are certain of.
The exploration and mapping of cell types and stages is a gigantic project that cannot be carried out by individual research groups. Large international collaborations have therefore been established, such as The Human Cell Atlas, which was founded in 2016.
The inventor behind this ambitious project is Kedar Natarajan's former research consultant, Professor Sarah Teichmann of the Wellcome Sanger Institute in England.
She was fascinated by the huge prospects of one day having identified all types of cells and their myriads of varying stages in the human organism. This will enable researchers to understand and treat diseases to an unprecedented extent.
In addition to The Human Atlas, Kedar Natarajan's research group also contributes to the pan-European research effort The LifeTime Initiative, which focuses in particular on developing new technologies for single-cell research.
– It's amazing to see so many different kinds of expertise contribute to this gigantic task: Researchers from many fields, including biology, physiology, epidemiology, chemistry, biophysics, data science and mathematics have joined forces and are investing an insane amount of resources into this task, says Kedar Natarajan.
The breakthroughs have already begun to show. One example is malaria.
Last year, Mara Lawniczak's research group at the Sanger Institute, with contributions from Kedar Natarajan, among others, announced the discovery of previously unknown types of cells responsible for the development of malaria.
However, since it’s only occasionally and under certain conditions that these cells actually trigger malaria, another interesting aspect is that the researchers were also able to pinpoint the specific conditions in which the cells became dangerous.
Kedar Natarajan and his colleagues at SDU are currently studying a gene found in most cells. Under normal conditions, this gene is harmless, but it can change, and in doing so, the cell becomes dangerous. Really dangerous, because the cell is now changing into a cancer cell.
– This gene is responsible for the development of most forms of cancer. Therefore, the fact that we’ve found the cell type that activates the gene and triggers the process that turns an otherwise healthy cell into a cancer cell could prove to be a huge breakthrough, says Kedar Natarajan.
This knowledge allows us to try to prevent the cell type from initiating the molecular chain reaction that leads to the development of all forms of cancer.
How can it be that it is only now that researchers have discovered that there are many more than 200 types of cells and that they can shape-shift into something almost unrecognisable?
It’s all a matter of perspective. 50 years ago, it made sense to assume that all cells in, for example, an organ such as the liver were more or less identical – or at least so similar that is was safe to assume that they behave in the same manner and react identically to influences.
Consequently, the characteristics of a liver cell were defined by, broadly speaking, blending a liver and then studying some of the cells that made up the blended mass to define what constitutes a liver cell.
What was not known at the time was that it was equivalent to emptying a fruit bowl into a blender: Sure, you get ‘fruit cells’ out of it, but you lose the level of detail and miss the fact that it originally contained many different cells from kiwis, bananas, apples etc.
– In the case of liver cells, we now know that there isn’t just one type. So far, we have defined 50 different types of liver cells, says Kedar Natarajan.
This revolutionary insight came when advanced technology made it possible to study individual cells to an unprecedented extent. Today, single-cell research is a rapidly developing field with high-flying ambitions.
In addition to The Human Atlas, other international collaborations are constantly working to analyse single cells to find new types of cells and new cell stages, which can contribute to our understanding of our organism and how to cure it when we become ill.
Contributions are also collected in e.g. Pediatric Atlas, Lung Atlas, Brain Atlas, Liver Atlas etc.
Are we home and dry once we’ve mapped every single cell type and stage?
– We will have solved that specific task. But then new ones will crop up. At that stage, we can start to look even deeper and, for example, address the individual molecules. Man's curiosity and desire for knowledge never stops, and therefore research never stops, either. We will constantly be searching further and deeper, Kedar Natarajan predicts.