Skin Cell Regeneration after Disease and upon Ageing
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| License | CC Attribution 3.0 Unported: You are free to use, adapt and copy, distribute and transmit the work or content in adapted or unchanged form for any legal purpose as long as the work is attributed to the author in the manner specified by the author or licensor. | |
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Transcript: English(auto-generated)
00:04
So I'm a cell biologist and I'm interested in regeneration of tissues and why in certain diseases and also upon aging, which relates to many diseases, why tissues are not able to regenerate as much as they can. Specifically we're actually interested into how cells that form the basis of tissues
00:24
and how the cell shape contributes to the regeneration of tissues and also maintains tissue function. Many tissues in the body, especially epithelial tissues, are what we call lifelong regenerating. That means that they renew themselves every so many days.
00:42
For example, the intestine will turn over in two to three days. Your epidermis of the skin is actually renewed every 20 to 30 days. This outer layer of the skin consists of many cell layers and this forms a barrier. This barrier protects this outer layer basically against water loss and that's why we can live on land but also against outside insults such as, for example, infection, heat or radiation.
01:05
We know that upon aging, because of this reduced regenerative capacity, this barrier doesn't function anymore properly. And what we are now trying to understand is really understanding how cell structure, how cells adhere to the other cells or to the environment that they lay down in proteins,
01:22
how this cell structure determines the regenerative capacity by looking at stem cells but also how it makes these final barriers and how it builds up these barriers. And that is what we do in my laboratory. So to address how cell structure determines tissue function and how it also allows tissues
01:44
to regenerate themselves throughout life to keep an epithelial barrier, we need to study these processes at different scale lengths. That means that we start at the protein-protein level and to understand how proteins interact with each other, to actually allow interactions between cells that are important for cell
02:01
shape. Then we take it into a cellular context where we now ask if we have these protein complexes and we take one component out, how does that affect the behavior of individual cells as well as cells in contact with each other. And then we have to take it to the next level where we basically, next scale level where we then look really in an organ and ask if we now remove one of these proteins
02:23
that we think is important for cell shape, what happens then at the tissue level and do we still are able to regenerate this tissue barrier and is the barrier function then still intact. Since cell shape is determined really by physical properties as well as biochemical properties and we know that force generation either within cells or tissues but also many outside influences
02:46
and the skin is a very nice example where you often rub your skin or you get compression or other types of when you flex that here you have a tension on the skin. So we actually collaborate then with both physicists and mechanical biologists to really
03:00
look at these different cells, at these different scale lengths basically how these processes function to really get a deep understanding how these tissue barriers renew and how they maintain while renewing their barrier function. By combining these physical, mechanical and cell biology approaches we basically have found
03:25
three main findings. One is that we now better understand how cell-cell interactions through cell adhesion receptors actually allow the cells to divide and renew the tissue by altering physical properties as well as chemical properties.
03:42
As a second finding we have that we now know that these cell-cell adhesion molecules integrate both physical cues, force cues, force generation cues as well as biochemical cues and that allows these cells to position the barrier exactly there where it's functionally required in the tissue to prevent water loss as well as help combat infections and
04:05
other outside insults. And the third finding that we have is that we now also know that biochemical signaling such as metabolic signals are not only important to allow cell division and cell shape changes but are also very important to directly generate key components of these barriers and that
04:26
allows them to contribute to the barrier. Why is it relevant what we're doing? So we know that in many diseases the skin barrier function is impaired. This goes for very inflammatory diseases which are very common such as psoriasis or atopic
04:43
dermatitis but this also goes in cancer or for example when you age that the skin barrier function is impaired. The old concept was that people thought that the skin barrier dysfunction was a consequence of disease and not a cause of disease but in recent years among others through our group we now know that the skin barrier function can be one causal effect of some
05:06
of these inflammatory diseases as well as directly contribute to cancer initiation and progression. One of our hypotheses is that we actually think that this skin barrier defect may not only be later making people prone for skin barrier diseases associated with type 2 diabetes
05:25
but perhaps in the other way that this may actually contribute to developing type 2 diabetes. At the same time we're also looking for example how the cell structure and this barrier function in skin cancer for example is altered and how this altered regeneration when you have too much cell division, too much regeneration and this can also happen
05:44
upon the aging. If those processes go out of control then you develop skin cancer and so we're trying to again understand how these aging processes that affect the skin barrier may then also contribute to developing for example skin cancer.
06:01
So what is the big challenge for us in the future? The big challenge is that we now understand on a single protein level quite a bit of what that protein can do but now we have to see this in the context of an integrated cell where a cell receives many different cues at the same time, both mechanical, physical as well as biochemical cues.
06:21
And this is then integrated by different protein complexes that have to be coordinated to allow the cell to change the cell shape and thereby also change its positions to start building these barriers. And I think this is of course also a temporal effect so we have to have better methodology to follow these processes over time but also better understand how these cues are integrated
06:43
and what are the key coordinators of these processes that allow these different complexes to coordinatedly change the cell shape and the cell position and allow cell division to regenerate basically. And one of the big challenges right now is that we can in cell culture can really look
07:04
and see what kind of mechanical cues are there and also exert forces on these cells but what kind of forces are really perceived when a cell is in the context of a living organism in a living tissue. This will be one of the challenges where we have to have also new methodology to start
07:21
to analyze this in an in vivo context and to be able then to control these forces in an organismal context basically.