New research update video with Prof. Ron Davis, March 29th 2021.
Huge thanks again to Ashley Haugen @AshleyHaugen88 for her hard work doing this, also to Ron and Janet.
@JanetDafoe
@DafoeWhitney
@CFSRC
#MECFS
Huge thanks again to Ashley Haugen @AshleyHaugen88 for her hard work doing this, also to Ron and Janet.
@JanetDafoe
@DafoeWhitney
@CFSRC
#MECFS
For patients that cannot watch or listen, I did a (rough) transcript below:
1 /21
-Intro from Ron. Ron's sole focus is ME/CFS.
-Trying to work on treatments or a cure.
-The Metabolic Trap idea. This is where a critical enzyme gets trapped in it's function.
#MECFS
-Intro from Ron. Ron's sole focus is ME/CFS.
-Trying to work on treatments or a cure.
-The Metabolic Trap idea. This is where a critical enzyme gets trapped in it's function.
#MECFS
2 /21
-Difficult to test in human cells, testing in bakers yeast. Have great technology for doing this.
-Have taken the bakers yeast and put in the critical gene that gets trapped (it's function gets trapped) and that is the IDO1 gene.
#MECFS
-Difficult to test in human cells, testing in bakers yeast. Have great technology for doing this.
-Have taken the bakers yeast and put in the critical gene that gets trapped (it's function gets trapped) and that is the IDO1 gene.
#MECFS
3 /21
-IDO1 converts tryptophan (amino acid found in diet) to kynurenine.
-Kynurenine is very important--can regulate the immune system, can suppress inflammation, possibly has a lot of other functions.
#MECFS
-IDO1 converts tryptophan (amino acid found in diet) to kynurenine.
-Kynurenine is very important--can regulate the immune system, can suppress inflammation, possibly has a lot of other functions.
#MECFS
4 /21
-Placing this gene into yeast they can control it, but it makes the same protein that is made in humans.
-Many of the human genes will work in yeast and vice versa.
-Yeast doesn't really have this level of pathway so kynurenine can be used to make NAD.
#MECFS
-Placing this gene into yeast they can control it, but it makes the same protein that is made in humans.
-Many of the human genes will work in yeast and vice versa.
-Yeast doesn't really have this level of pathway so kynurenine can be used to make NAD.
#MECFS
5 /21
-NAD is chemical compound that is used extensively in metabolism of organisms, humans and yeast.
-In humans NAD is used in about 400 chemical reactions, really essential.
-Absolutely required for the production of energy in the mitochondria.
#MECFS
-NAD is chemical compound that is used extensively in metabolism of organisms, humans and yeast.
-In humans NAD is used in about 400 chemical reactions, really essential.
-Absolutely required for the production of energy in the mitochondria.
#MECFS
6 /21
-What they have done is make kynurenine in yeast with this enzyme and then require it to make NAD.
-Yeast has multiple ways to make NAD so have removed all the genes involved in the production of NAD.
-So the ONLY way yeast can make NAD is to have this pathway on.
#MECFS
-What they have done is make kynurenine in yeast with this enzyme and then require it to make NAD.
-Yeast has multiple ways to make NAD so have removed all the genes involved in the production of NAD.
-So the ONLY way yeast can make NAD is to have this pathway on.
#MECFS
7 /21
-If they trigger the Metabolic Trap which will shut down the enzymatic activity of IDO1, then it can't make kynurenine, and then it can't make NAD. If it can't make NAD, it can't grow.
#MECFS
-If they trigger the Metabolic Trap which will shut down the enzymatic activity of IDO1, then it can't make kynurenine, and then it can't make NAD. If it can't make NAD, it can't grow.
#MECFS
8 /21
-Technically one problem is they don't want the yeast to consume tryptophan by any other pathway.
-Have looked into yeast, all genes have been sequenced and they understand their function, have found several genes that consume tryptophan for other purposes.
#MECFS
-Technically one problem is they don't want the yeast to consume tryptophan by any other pathway.
-Have looked into yeast, all genes have been sequenced and they understand their function, have found several genes that consume tryptophan for other purposes.
#MECFS
9 /21
-They have removed these genes.
-This new developed yeast is now suitable for a test.
-Grew yeast on low tryptophan, the cells grew fine.
-If they raise the tryptophan concentration, the high level of tryptophan can inhibit the enzyme.
#MECFS
-They have removed these genes.
-This new developed yeast is now suitable for a test.
-Grew yeast on low tryptophan, the cells grew fine.
-If they raise the tryptophan concentration, the high level of tryptophan can inhibit the enzyme.
#MECFS
10 /21
-This is very strange.
-Here is an enzyme that converts tryptophan to kynurenine. You would guess that if you raised tryptophan it would simply make more kynurenine.
-That's not true. High tryptophan inhibits the enzyme and it can't make kynurenine.
#MECFS
-This is very strange.
-Here is an enzyme that converts tryptophan to kynurenine. You would guess that if you raised tryptophan it would simply make more kynurenine.
-That's not true. High tryptophan inhibits the enzyme and it can't make kynurenine.
#MECFS
#11
-If it can't make kynurenine it can't grow--so if they raise the concentration of tryptophan it gets to a point where it will stop growing.
-So as long as tryptophan is left in there at a high level, it can't grow.
#MECFS
-If it can't make kynurenine it can't grow--so if they raise the concentration of tryptophan it gets to a point where it will stop growing.
-So as long as tryptophan is left in there at a high level, it can't grow.
#MECFS
#12
-If you wash out the high level of tryptophan + put in low level of tryptophan, it starts growing again.
-OR if you leave high level of tryptophan but give yeast kynurenine it starts growing again, even in presence of high tryptophan + absence of enzyme activity.
#MECFS
-If you wash out the high level of tryptophan + put in low level of tryptophan, it starts growing again.
-OR if you leave high level of tryptophan but give yeast kynurenine it starts growing again, even in presence of high tryptophan + absence of enzyme activity.
#MECFS
13 /21
-Why are they doing all this?
-To test Metabolic Trap--something that works in a test tube--does it work in a cell?
-This experiment shows it CAN work in a cell. It's yeast, but can still work in a cell.
-Encouraging, this is a possibility happening in humans.
#MECFS
-Why are they doing all this?
-To test Metabolic Trap--something that works in a test tube--does it work in a cell?
-This experiment shows it CAN work in a cell. It's yeast, but can still work in a cell.
-Encouraging, this is a possibility happening in humans.
#MECFS
14 /21
-Another reason to do this. Now have system where they can shut down enzyme in Metabolic Trap + only way the cell can grow is to get rid of tryptophan.
-Human cells not quite the same, it's not growth, it's kynurenine which is critical factor.
#MECFS
-Another reason to do this. Now have system where they can shut down enzyme in Metabolic Trap + only way the cell can grow is to get rid of tryptophan.
-Human cells not quite the same, it's not growth, it's kynurenine which is critical factor.
#MECFS
15 /21
-If this was true in human cells the only way to make kynurenine would be to get rid of the tryptophan. Only way to get rid of tryptophan is to convert it to kynurenine.
-That's why it's called a trap, you get into it, you can't get out.
#MECFS
-If this was true in human cells the only way to make kynurenine would be to get rid of the tryptophan. Only way to get rid of tryptophan is to convert it to kynurenine.
-That's why it's called a trap, you get into it, you can't get out.
#MECFS
16 /21
-However if they find compound that will 'block the block'--the inhibition that tryptophan has over the enzyme, then will reactivate IDO1, then IDO1 will consume the tryptophan and the cells will produce kynurenine.
-That's the stage are at the moment with yeast.
#MECFS
-However if they find compound that will 'block the block'--the inhibition that tryptophan has over the enzyme, then will reactivate IDO1, then IDO1 will consume the tryptophan and the cells will produce kynurenine.
-That's the stage are at the moment with yeast.
#MECFS
17 /21
-Fairly simple to do with yeast. Put it in high tryptophan and can add drug(s) at different concentrations + look for growth.
-Have a robot that can do all this. Can do 96 at a time and have 3 robots. Can do this with different concentrations of drugs.
#MECFS
-Fairly simple to do with yeast. Put it in high tryptophan and can add drug(s) at different concentrations + look for growth.
-Have a robot that can do all this. Can do 96 at a time and have 3 robots. Can do this with different concentrations of drugs.
#MECFS
18 /21
-Can set this up and leave it to do experiments. Being set up now.
-Unfortunately robot over a decade old and needs repairs. However are getting help and is getting fixed.
-Just about ready to do drug screening.
#MECFS
-Can set this up and leave it to do experiments. Being set up now.
-Unfortunately robot over a decade old and needs repairs. However are getting help and is getting fixed.
-Just about ready to do drug screening.
#MECFS
19 /21
-Have all FDA-approved drugs in their freezer. Have screened all + know effect on yeast and know concentration that has some effect.
-Ron excited by this, has no idea what the probability is but is optimistic. Lots of things to try at different concentrations.
#MECFS
-Have all FDA-approved drugs in their freezer. Have screened all + know effect on yeast and know concentration that has some effect.
-Ron excited by this, has no idea what the probability is but is optimistic. Lots of things to try at different concentrations.
#MECFS
20 /21
-If FDA-approved drugs don't work out, will start screening herbal extracts. Has been in contact with people in China + India for this.
-Wants to have something patients can take, a new compound would take updated approval + years to do, doesn't want to do that.
#MECFS
-If FDA-approved drugs don't work out, will start screening herbal extracts. Has been in contact with people in China + India for this.
-Wants to have something patients can take, a new compound would take updated approval + years to do, doesn't want to do that.
#MECFS
21 /END
-Optimistic can find something. If Metabolic Trap is real then they have something to treat it with.
-Next thing is moving to human cells. In process of doing that.
-Ron says thank you.
#MECFS
-Optimistic can find something. If Metabolic Trap is real then they have something to treat it with.
-Next thing is moving to human cells. In process of doing that.
-Ron says thank you.
#MECFS
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