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[Music]

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Hello and welcome to a

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new interview in medical physics.

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In the video, we meet Michaela.

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She is a PhD student here at the

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German

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Cancer Research Center and I will meet

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her in a laboratory. Therefore,

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we have to leave the building where I

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am right now. So, let's

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go and meet here there.

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[Music]

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Hello. Hello

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Michaela. Nice to have you with us.

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Thank you! I just

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mentioned that we are now going to the lab,

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but maybe you can first briefly

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introduce yourself. Of course. I'm a PhD student

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in applied medical physics,

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but my project is 

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a bit more towards

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radiation biology. I work, so to speak, at

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the interface between physics and

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biology. Ah okay, so now we'll learn

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a little more about the biological

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side and not just the

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physics side. Can we just

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go into the lab or do we have to

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consider something? If you

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work in the laboratory, you need a

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safety training and that means

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that you have to wear protective clothing

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So first we have to put on a

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coat and then we can

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go in. Okay, let's do that

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then.

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[Music]

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Done and ready to go! Exactly! 

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Come on! What are you working on

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at the moment? I have two

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major projects at the moment, one of which is a

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long-term project. I'm investigating the

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dose effect of different

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radiation types, and the goal of all this is for

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my tumor model to determine the curative dose to

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and when I've found it

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I look at the short-term effects

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especially at the histological level,

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almost after different points in time after

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the irradiation and see exactly what

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happens in the tissue, what the

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structural changes are and how

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the tissue reacts to the radiation.

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What can we see here in the

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laboratory? First of all,

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I would now simply show you how

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I prepare tissue sections, which are, so to speak,

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the basis for my research.

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To do this, we sit down in the cryotome.

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[Music]

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So, the goal of the whole thing is to

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have thin cuts of the

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tissue. In this case, they are now 7

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micrometers in thickness, 

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so really, really thin, and there are

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different methods. I'll show you

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how I do it.

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I've already prepared the tissue. 

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I cut off this piece a bit

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to get a fresh piece of tumor.

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Then I ensure that the area down here

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is completely clear.

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And in here, there are minus 20° degrees Celsius

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and up here, of course, there is

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room temperature. 

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I will show you how it works. 

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It will now go down very slowly 

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to cut a very thin piece.

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.

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You need a bit of instinct.

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Here is the piece

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which we can pull forward

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very carefully 

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with the brushes.

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We need to be careful in order not to rip the piece.

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Then, there is our object carrier

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at room temperature, then we place the piece on it. 

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And that's our first slice

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to start staining. 

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This is a prostate tumor, which you can

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seen here. For example, you can also see a

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a bit of blood accumulation and vessels and

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this tumor is also known for

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lymphatic fluid and that is

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here the white mass that you can see.

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You can also see different structures, which we

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will take a closer look at under the microscope.

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You have cut

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the very thin layer of the tumor.

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What is the next step,

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what would come next?

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So in the next step, we would

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stain the section with an

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immunohistochemical staining. 

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We use antibodies to look at a

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specific target molecule and

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this is then usually coupled to a

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dye or a fluorophore and

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we can then look at it under the microscope.

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I have already

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prepared some slices

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There are various holders here.

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This is the cut with

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three different tumors. I have

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marked them for me so that I know 

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where they are.

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This is our microscope.

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Let's turn on some light.

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Is there a reason why it is

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so dark in the room? Does it have to be like that?

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Yes, indeed.

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The pieces we prepared

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are light-sensitive, 

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so they should not get in too much

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light, because otherwise our

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fluorophores would bleaches out

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and we wouldn't see it anymore, 

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and also for the computers is better to see the contrast

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on the images on screen. 

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Let's turn it on here. 

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First, I select the ocular

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to find the tissue. 

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Maybe you could already

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see something.

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This is the device 

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to virtually move over the piece. 

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When we are sure that

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we have also focused on the focal plane,

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we can transfer everything

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to the computer.

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What we can see in blue

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are the cell nuclei of the tissue. 

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When we have done the

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recording, I stop it right now. 

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Then we can zoom in. 

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We can really see 

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the different cell nuclei in

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the tissue.

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This is basically the first channel.

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What I usually do then,

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what we can see here,

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once we took the shot from all levels,

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the channels are in

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several colors. Here again in blue the

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cell nuclei and in green we can see the

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marker Palemonidosol.

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This is activated

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by a redox reaction when

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the oxygen content in the cells is very low.

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Therefore, we now know, 

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that hypoxia exists in these cells,

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meaning that there is a very low

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oxygen concentration and these cells

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are normoxic here and this is

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particularly very relevant for radiotherapy

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because oxygen

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intensifies the effect of radiation

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and that means that these

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cells tend to be more difficult to treat.

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What we see here in red

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are the

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blood vessels or vessels in general,

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stained with CD3. You can see here 

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that the tumor tends to have a fairly

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chaotic vascular system. Vessels that

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simply end somewhere in the middle of nowhere or

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that are also sometimes very small, 

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which is characteristic of tumors, while

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normal healthy tissue has a very

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systematic vascular structure and that

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actually also leads to

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these low-oxygen areas.

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We can see that down here

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because they tend to

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be at a certain distance from the

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vessels. Or what can also be the case is that

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we have non-functioning vessels

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like here, because they are in the middle of this

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green area, so hypoxic,

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with low in oxygen concentration, meaning that the

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tissue around it is not being properly supplied.

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This is all tumor tissue,

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but of course a tumor does not only

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consist of tumor cells, it also has

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supporting cells that supply it,

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but we can not directely see these cells on the picture, 

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for that we would have to use

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a different staining method. Thank you,

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Michaela, for giving us an insight into your

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research. My pleasure. Now a provocative

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question: in medical physics you work

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also work a lot with

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simulations. Do they then need your

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radiation biology research at all,

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if you can actually simulate everything somehow?

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Is it really necessary? 

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That is a legitimate question.

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There has been a lot of progress in that regard,

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for sure. You can do a lot of

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simulations, but the basic principle is

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you first have to understand what

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happens exactly in the biological

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tissue, how does tissue react to

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different beam types, do they trigger the

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same pathways or different

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signaling pathways, and simulation also

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always needs a certain amount of basic information

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and we try to create that

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to improve simulations and 

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to integrate them into research.

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This is the schematical 

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chain of

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radiotherapy. Where would you

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assign your research

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on which chain?

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On which side?

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This is the classic

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clinical workflow for patients. Due to the fact that

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I don't have direct contact with patients

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it is of course a bit

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more difficult. I mean, I work in the

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preclinical area and overall,

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the idea of my research is to 

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optimize the treatment, so I would

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probably tend to assign my research here,

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but probably

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a bit more far away, 

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because the goal of my research

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is ultimately to

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understand what the radiation does in the

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tissue, are there differences between

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e.g. photon or between

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particle radiation and we can

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then have a look at it on the fluorescence images

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and I think it then makes a final contribution

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to improve the treatment of patients.

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What is the most 

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fascinating part of your project

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you work on?

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There are many different

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fascinating things.

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Perhaps a special highlight?

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Well, I would say that

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that the fluorescence images are very

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fascinating, that it just

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works, that we can look at markers

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and if we think about it

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you've seen the tissue on

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this slide, but we can

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really zoom in to the cellular level

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in the microscopy and then really

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look at. We even have the

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ability to visualize DNA damage

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in the cell nucleus and

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I think that's pretty remarkable.

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What are your

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maybe very

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personal tips for someone who

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is considering entering the field of medical physics

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or radiation therapy.

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Why should someone consider this area

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from your point of view? 

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I find it a very exciting topic. Above all, it is

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also very interdisciplinary, which is also

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the reason why I am in this field. 

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My background is that I

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studied biophysics, and I knew from the beginning

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that I wanted to look at different

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subject areas and 

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I also had the possibility during my study

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to do so.

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I actually had my first contact with medical physics

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during my

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bachelor thesis, which I did

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at the Society for

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00:11:04,720 --> 00:11:06,480
Heavy Ion Research in Darmstadt at the time. 

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That was my first contact

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with the field. In the

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00:11:09,839 --> 00:11:11,279
master's thesis, I again tended more towards

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pharmaceutical biology, but for the

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doctoral thesis I wanted to

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combine everything, and for me it's just

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a nice interface between

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physical applications and

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00:11:19,519 --> 00:11:21,800
biological know-how that

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comes together.

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[Music]