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In order to fit through small capillaries, red blood cells expel their nucleus and degrade their organelles. Professor Simon's studies show that autophagy is responsible for the degradation of organelles in red blood cells, in particular mitochondria. Lack of autophagy in these cells leads to their cell death and anaemia.

Q: Hello Katja. What is autophagy?

KS: Autophagy is a cellular process in which the cell degrades its content, its toxic waste. And among that toxic waste there can be organelles like mitochondria, but also big protein aggregates. It is very important to degrade toxic waste for the survival of the cell and it has been shown over the last five years or so that a cell without autophagy cannot survive, so it is important for survival. But it has also been shown that it is important in disease development, like Parkinson's disease, which is characterized by the accumulation of protein aggregates in neuronal cells. And furthermore in the aging process it has been shown that autophagy levels fall, and the whole idea that we age, including wrinkles, hearing loss, cancer, and these things that occur with age are actually due to these falling autophagy levels and accumulation of toxic wastes in the cells. My lab is interested in white and red blood cells, and the role of autophagy in these cell types.

Q: Why is autophagy so important for our red blood cells? What happens when this mechanism does not work properly?

KS: Red blood cells develop from a mature cell which, just like every other cell, has got a nucleus and has got organelles and so forth, into an empty sack which just carries hemoglobin to the different parts of the body. These red blood cells have to fit through small capillaries, and they can only do that if they get rid of all their cargo, all their nucleus and mitochondria, and then will die shortly after that. But in that process they can carry the oxygen to the small capillaries. When autophagy does not work in these cells, we have found in our models that the red blood cells do not mature properly, and are still able to expel the nucleus, but the other organelles (in particular the mitochondria) are no longer expelled. Basically in our models we find that the lack of autophagy leads to anaemia which is the lack of these red blood cells to develop and do their normal function. We are actively researching into whether this is true in certain human anaemias and whether human anaemias can be due to the lack of autophagy.

Q: What is the most important lines of research that have happened in the last five or ten years?

KS: I would say that autophagy's playing a role in many diseases, but one of the diseases which we don't know very much about yet and is actively researched in our labs and in others, is the role of autophagy in cancer. We don't yet really understand whether autophagy is needed for survival of the cancer or not. Our models show that the lack of autophagy, particularly in white blood cells, leads to an accumulation of toxic waste, which then leads to DNA mutation transforming these white blood cells, for example into a leukemic cells. Later on these leukemic cells will require autophagy to survive, but a lack of autophagy might be the cause for the initiation of the transformation into leukemic cells. We are actively researching into this field too; we are trying to find out whether human leukemia has got something to do with the loss of autophagy.

Q: Why does your line of research matter? Why should we put money into it?

KS: I think it would be very important to understand how drugs that are currently used in cancer, although we know that they modulate autophagy, whether that is good or bad, whether they should be inhibiting or promoting autophagy. Also this is a very novel field, and none of these connections have been made before, for example that leukemia could be caused by a lack of autophagy. It is extremely important to figure that out, because that could really lead to a cure for these diseases, or at least to a better use of the current drugs and novel drugs which are being developed.

Q: How does your research fit into translational medicine within the department?

KS: On top of the basic research we are doing in this field, we're also heading a translational immunology lab which helps other scientists in the department and other departments of Oxford University to measure immunological parameters, and autophagic parameters. This entails having some high state of the art technology, which is quite difficult to operate oneself. We are helping scientists to operate these machines, and to set up their assays, to analyze their data. It has proven very successful as a lot of people are using it now, and this is to do with Parkinson's disease, HIV, and lots of other diseases which we are particularly interested in. We are a kind of hub where the scientists come together!

Katja Simon

Autophagy

Autophagy is the cellular process in which cells degrade their toxic waste and damaged organelles. Professor Katja Simon studies how the lack of autophagy seems to trigger DNA mutations and the development of leukemic cells. This might help us make better use of current therapies and develop new ones.

This podcast presents the research done by Professor Simon whilst working in the Nuffield Department of Medicine. Professor Simon now works at the Kennedy Institute of Rheumatology.

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