Christina Harris

Explore the Future

Tina Arnall

Rachel Nelson

Milka Rojas

Starting with Jesus

14 Revelation 10 & 14

Advent HOPE Sabbath School

Consciously Uncoupled

Dear Father in heaven, I thank you for this afternoon.

I thank you for how you have guided each 1 of us to where we are at in life right now, and we just ask that you would be with me now as I speak.

Please bring to my mind the things that should be said and help me to say it the way you would want me to say it.

Speak through me and please minister to each 1 here as well as you minister to me.

So the title is Consciously Uncoupled and I told you this morning if those of you were here that it's probably not what you think.

So I was traveling in Europe, It's probably been quite a while ago, and we were traveling by train between Vienna and Salzburg and When we were going on The train announcer I didn't speak German, but the friend I was traveling with did and He was they were saying something he goes.

Oh, we're on the wrong We're in the wrong part of the train And so we had to get up get our bags and move quickly to another part of the train because the train was going to uncouple From the other 1 and that's just where they separate from each other and this train goes that way and I guess the rest of it goes another way and they just part amiably and so they're going different directions so they separate.

When you have the citric acid cycle, that's 1 of the first cycles that pretty much everything in your body kind of turns around that.

And it's just 1 of the ways that your body turns food into energy.

You might eat something, let's say you have some carbohydrates, those go through glycolysis And then that goes through the product of glycolysis, goes through the citric acid cycle.

And then once it's done with the citric acid cycle, it will enter those little blue blobs up there.

And it's possible to uncouple those 2 processes.

And that's what I'm going to be talking about some today.

And here's just a little video of that taking place.

From the citric acid cycle, you are making NADH and FADH2.

And those protons from there or hydrogens from there move through the electron transport chain.

The electrons move through and the protons move across the membrane So just like you're charging a battery, right you charge a battery Well, you you have a battery and it has a discharge potential and you're just letting it slowly discharge here You're charging the battery by sending the electrons through and you're sending the protons through at the same time so that you get a lot more protons on 1 side than the other side and then your body does work by just letting those pass back across the membrane but they have to pass through the little pink thing at the bottom which is the ATP synthase.

It gets uncoupled when those protons move across the membrane, but not through that enzyme.

We will talk more about that, but this is going to be a video here and you can see hopefully it works here.

So, you have the FAD and the NADH2 are moving there and they're passing their hydrogens, the electrons move through the transport chain and the, well the electrons move through the transport chain and the hydrogens move across.

And you can see they're getting a little bit more there But then they're coming back through through the little pink ATP synthase at the bottom 3 of those hydrogens have to move through to make 1 ATP molecule And that's the currency that your body uses for energy.

That can get uncoupled when you have certain kinds of molecules or something like that which can help the hydrogens move back through, but not through the ATP synthase.

Your body also lets some of that uncouple naturally.

That's what keeps your body temperature up through just thermogenesis.

But that uncoupling is what I want to talk about today.

Okay, so we have the citric acid cycles what feeds into that and that's called a cycle because it doesn't really have a beginning or an end You have molecules that are entering at any point in the in the cycle and so our whole metabolism pivots on the citric acid cycle and that metabolism So that's also called the Krebs cycle or the TCA cycle depending on when you when you learned it if you've learned it And it's central to our metabolism it's 1 of our major sources of energy that NADH that comes from there and the FADH2 are kind of like a currency and then you exchange that currency for ATP in the electron transport And the citric acid cycle was elucidated by Hans Krebs back in 1940s and 50s and he won the Nobel Prize for that in 1953 and Then the citric acid cycle is always taking and it's always giving.

If it stops giving it can't take anymore.

That's kind of interesting and if it keeps giving it can keep taking but if it stops giving it can't keep taking.

So it's really controlled for the cycle to keep running it has to keep giving and taking.

And that's something that I'll mention more later.

So like I said Hans Krebs was the 1 that discovered that and elucidated the mechanism of that and he submitted his paper to the journal Nature back in the, I guess the early 50s or the late 40s And they responded to his submission with the note that they already had plenty of publications to get in before the end of the year and that if he wanted to get a timely release of his research he should send it to another journal.

So he sent it to another journal and then it was submitted and they accepted it quickly and they published it within a few months.

But that was a paper that was responsible for his Nobel Prize that he won in 1953.

So they missed a big opportunity to have a Nobel Prize winning paper in your journal is a pretty big deal and they missed that and he says that was the first time in his career after he published about 50 papers that he got a rejection or even a semi rejection.

They said well if you want to you can resubmit it after this time period and we'll look at it again.

And so it was about 30 years later, 25 years later, maybe I guess it's 50 years, that the journal Nature published this in their 1988 edition, 1 of their articles.

They said, an editor's nightmare is to reject a Nobel Prize winning paper.

Rejection of Hans Krebs' discovery of the tricarboxylic acid cycle or the citric acid cycle or the Krebs cycle, a pivot of biochemical metabolism remains nature's most egregious error as far as we know.

And so they were a little late with that, and they missed a big opportunity.

But if you think of there are other opportunities where people have missed something that was really big that was right in front of them and they didn't catch it.

I think 1 of the biggest ones that I can think of in earth's history is to have Jesus living right among you and missing it, like the stone that the builders rejected.

They said that was the cornerstone and he was missed.

And Peter was saying that in the book of Acts to the people there that were gathered in Jerusalem around the time of Pentecost.

He says, let it be known to all of you and to all the people of Israel that by the name of Jesus Christ of Nazareth whom you crucified, whom God raised from the dead, this Jesus is the stone that was rejected by you, the builders, which has become the cornerstone.

And the message that he brought, there have been other times when people have missed things.

But he missed other opportunities before that.

There's a story of when the Jewish leaders came to Peter and said, do you and your master pay the temple tax?

And in saying that, Peter was saying that Jesus wasn't really divine.

Ellen White says, in Desire of Ages, that Peter just a little bit before that had said and spoken out loud that Jesus was the Messiah.

But by his answer to the collector that Jesus would pay the tribute, he had virtually sanctioned a false conception of him to which the priests and the rulers were trying to give currency.

So he missed an opportunity to honor Jesus.

And that wasn't the last time that happened.

But moving on, so looking now, that was the citric acid cycle and it feeds into electron transport.

And that is where you're exchanging your NADH and your FADH2 for ATP.

And that gets its molecules from the citric acid cycle and then you're making energy.

Okay, and those 2 processes need to be coupled.

What's getting made in the citric acid cycle needs to couple to the electron transport chain because if that uncouples, that can be very bad.

There's a lot of, they figured out a lot of how the citric acid cycle and how electron transport works with a lot Of different drugs that will short-circuit a electron transport at different places Some of those are like rat poisons and stuff.

So it's It's quite effective, an effective way to bring about death, I guess.

So here, what can happen is if you're able to send back the protons where you're not going through the ATP synthase, that's called uncoupling.

And that energy that would be used to make ATP to do work is instead sent past the membrane.

Now If you have a battery and you plug it into a load, let's say we have a battery, we have 2 terminals, we plug it in and we close the circuit and we have it running through a light bulb.

When we have the circuit closed, what happens?

The light bulb comes on and you're doing work, you're moving electrons through there, you're getting the light bulb, you're also generating some heat too, right?

So when you have that circuit closed and it's coupled, when the battery is coupled to its load, then you're doing work.

But what if I were to take the battery and I took the 2 terminals and I just touched them together?

Then you're just generating heat and you're not doing any work.

So you can think about that in different scenarios.

I think of it often with the church when we're not doing work, sometimes we generate more heat than doing work.

And that can happen when we're uncoupled.

And that's kind of what I want to talk about today.

So it's just like that battery as long as you have it plugged in where you're doing some work and you have a load that's there then you can do something productive but when you take it off and you short circuit the battery then it's going to keep consuming.

So when that gets uncoupled between citric acid cycle and electron transport, the body compensates.

It just keeps on breaking down glucose because there's a call for ATP, but none is forming.

So we just keep on sending more and more and more and more there.

So it breaks down fats, breaks down the glucose, the temperature of the body increases, fatigue ensues and blood sugar drops and then that's when it can be bad.

They're still looking at how to use this for weight loss.

It was used for weight loss for a brief period of time at once because it's kind of a good idea.

The bad thing is that there's such a narrow window of therapeutic activity.

If you go a little bit over, It can be disastrous.

Like, you know, you have Tylenol, and you're like, I have a headache.

Folded

When it doesn't dissolve in the water very well, well, the hemoglobin that has the faulty protein in it that has the wrong amino acid, those red blood cells are kind of sticky.

And that's because you put the valine there instead.

It's sticky, and so when it gets, there's not enough water and the person is not hydrated enough those kind of clump together and then that prevents getting good oxygen flow and then it causes pain in the muscles and stuff.

So that comes from just having 1 point mutation in the amino acid and that can lead to crisis.

So these different chaperones are responsible for a lot of different things that need to happen in the body.

First they help to get a protein folded de novo like we saw on the screen.

Just as it's being synthesized they can help the protein to fold there.

They can also refold a mature protein, 1 that's already got its shape.

If there's some kind of stress that's put on the cell or the body, the system, then it can help to refold it into the right shape.

And it also ensures that terminally abnormal proteins are marked for destruction so that they can clear those away.

So it's kind of neat all those different parts that these chaperones play.

And so 1 of the first lessons I learned when I was looking at this is that chaperones provide a solitude place for proteins to find the right fold.

You can see when it went into that little chaperonin, then the door shut and it's just that protein that's there.

Now the chaperonin itself is a protein, Okay, and it helps other proteins to fold and then you can ask you can kind of think of that It could be a question for origins which came first right the chaperone that helps the protein to fold or you know So that that's a conundrum if you're trying to promote some certain philosophies So it's easier for the protein to get the right fold when it's surrounded by the right environment.

And God does that in our lives and I can see a place in scripture where God did that for someone else.

You remember Moses was in Egypt and he was there for 40 years and then he learned a lot of things while he was there.

And then God sent him to the desert for 40 years because he had to unlearn some things where he was surrounded by a culture that was fully pagan.

And in counsels to parents, teachers and students, it says, but the most valuable part of Moses fitting for his life work was that which he received as a shepherd.

In the solitude of the mountains he learned that which all his instruction in the king's palace was unable to impart to him.

Simple, unwavering faith and a constant trust in the Lord.

When Moses was in Egypt, he had everything that money and education could buy.

And as far as the Egyptians understood it.

There's something else you need in order to be complete in me, and there's some things that you need to get rid of in order to be complete in me.

And she continues in conflict and courage, in the solemn grandeur of the everlasting hills, he beheld the majesty of the Most High and realized how powerless and insignificant were the gods of Egypt.

Everywhere the creator's name was written, Here his pride and self-sufficiency were swept away.

The results of the ease and luxury of Egypt disappeared.

Moses became patient, reverent, and humble, yet strong in the faith of the mighty God of Jacob.

So Moses was up all alone guarding sheep and he learned a lot there.

There was no worldly grandeur and God had to help him to undo some of the things that he'd had in his life there.

And God gave me some solitude before I became a Christian, or right as I was becoming a Christian.

I had moved away from home, and I did my PhD at University of Colorado, and then I had gone to New York, to Manhattan, and I was doing a post-doc at Sloan Kettering.

And right before I left, someone had given me a study guide on the book of Mark and I really before that time when I looked at the Bible I didn't understand it really well and I tried to do devotions and it just was like it wasn't working.

And so when I got to New York, I was kind of all alone.

And I started to get out that study guide, and I started to read it with my Bible.

And that was the first time I remembered where God was really speaking to my heart as I was studying.

And then I, for some reason, I decided I wanted to study some more, and so I Googled, or Yahoo'd back then, Daniel and Revelation, a Bible study.

And there was an Adventist physician in North Carolina that had this site where he would, you could study the Bible and you kind of, you did internet back then, but it wasn't fully electronic.

So he would send me the Bible study guides and I'd respond by email.

And I was doing those third Daniel and Revelation seminars and I would always kind of just go through.

I was mostly just interested in the information and you get you know the end of all those Bible studies at the end It has this question right your decision question So I never answered those because I didn't think it was important and the guy that was giving me the Bible studies He goes I noticed you didn't answer that last question he says I'll save you the next study guides when you do.

And so I started answering the last question so I could get the Bible study guides.

And eventually after that I was baptized.

I've watched a video downlink in New York City where I was at.

Actually I took the train to Queens every night and somebody later told me that probably wasn't the best thing to do but I always felt pretty safe.

So then after that I was baptized in New York and it was also called Advent Hope, the church that I went to.

It's called the Church of the Advent Hope.

It was a German church, and right there in front of the 2 double doors, it's written in German, Church of the Advent Hope.

And right after that, very same day, I broke my femur.

And I was in the hospital for 2 weeks and then in like a rehab for a couple weeks.

And I really grew to appreciate physical therapists And it really helped.

But just because we give our hearts to God doesn't mean that no disappointments are ever going to come to us.

But that was also a time where I could have some downtime and study more.

After that, all I wanted to do was study the Bible and so I had a month of just studying the Bible.

God gave me that solitude and that's what the proteins need too.

So another thing I learned about the proteins was that misfolded proteins cause disease.

And so when you have the Alzheimer's, the plaques that form, those cause disease and you can see up there is kind of a slide of that.

And You can see here is another protein folding diagram.

I don't know if you've seen these before, probably some of you have not.

Up here you can see at the top of it, it says unfolded.

That's a protein that doesn't have any fold yet.

It's probably just come off the ribosome.

The further down you go, the lower in energy.

1 of those energy levels is where the protein has its native form and the native form is what it should look like.

And so over there on the green part is the native state.

And on the other side, you can have some, you can see the red part where it says amorphous aggregates.

So you can have, if the proteins don't have the right fold, they kind of all stick together, kind of like bread dough.

If you have bread dough, they'll kind of stick together, those pieces.

And that's what happens when a protein is misfolded.

It's parts that are sticky in water are on the outside and the parts that should be exposed to water are on the inside.

So That happens and then sometimes in the case of Alzheimer's, you'll have these little amyloid fibers start to form, or the plaques.

And those are really rigid, they're very stable, but it's a terminal stability, 1 that's not healthy.

And so when you have those, a misfolded protein can lead to disease.

And some other examples of types of diseases that are caused by protein misfolding, we already mentioned sickle cell anemia.

There's also cystic fibrosis in that protein that's coding for a conductance regulator which kind of controls the flow of chloride ions in and out.

There's a single amino acid that's been lost, a phenylalanine.

Another example, are there some of the neurodegenerative diseases like I just pointed out, Alzheimer's, Parkinson's, Huntington's disease, and then also if you've heard of mad cow disease, it's a similar problem that results.

And so those are all kinds of diseases that result from proteins misfolding.

And we also get misfolded early on in life sometimes.

And we get off on a wrong trajectory and it takes us where God didn't want to take us.

And you can think of Paul and his life, he was very zealous for what he was doing.

In Acts chapter 8 it talks about Paul going around ravaging the churches, getting permission to bring people to jail and commit them to prison.

And then we see that God had to get his attention before he could bring anyone to help him.

A chaperone at that time would probably have been destroyed by Paul so he had to tame him down and disarm him first before he could get some instruction.

And so Ananias comes to Paul and helps him to get the right fold.

The Lord said to him, Go, for he is a chosen instrument of mine to carry my name before the Gentiles and the kings and the children of Israel.

For I will show him how much he must suffer for the sake of my name." And so Paul was brought into the fold and we all get people in our lives that kind of bring us to God.

It's not all on our own and you know I just read the Bible and I suddenly get it.

He has people in our lives and so I think I left home misfolded.

Plum Pudding and Things We Believe

Like Esther said, my name is Christina Harris and I'm at Weimar Institute.

I'm a chemistry, my PhD is in organic chemistry and I'm the chair of the natural science department at Weimar Institute.

This is my seventh year there and I enjoy teaching.

And the title of my talk this evening is plum pudding and things we believe or things we believed.

It depends on how you want to think about it.

I try to make it where it's understandable to most people so I hope you are able to follow.

So this is a picture of a man named JJ Thompson and he is the 1 that's credited with discovering the electron.

And he won the Nobel Prize in physics in 1906 for this discovery that he made in 1897.

And so it's right near the turn of the going into the 1900s and can you remember when Darwin's book that he wrote on the the 1 that we when he wrote that's so famous?

Origin of species and that when was that written.

So that's interesting that we didn't even know there was an electron when he made those proposals.

And then you think of all the things we've learned about science since that time, they were still figuring things out.

They didn't even know what the structure of DNA was when he proposed that, made that proposal of how things came about for origins.

And so it's kind of interesting to see how much farther we've come since then.

And if you were going to think about the size of an electron if you had a penny and a bowling ball That's the relative Ratio between an electron and the proton the protons are where out in the molecule.

I mean in an atom Yeah, they're in the they're in the middle in the nucleus and the electrons are on the outside.

So the proton is much, much bigger and J.J.

Thompson even said, he said, could anything at first sight seem more impractical than a body which is so small, talking about the electron, that its mass is an insignificant fraction, 1 3, 000th, of the mass of an atom of hydrogen, which is essentially a proton.

And so you would think that that sounds pretty impractical, but actually electrons govern how molecules react.

They're really small, but they're 1 of the more important parts, although you need all parts.

And then you can think about, you could have said, could anything so small make a difference?

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Christina Harris

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14 Revelation 10 & 14

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Consciously Uncoupled

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Folded

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Consciously Uncoupled

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Plum Pudding and Things We Believe

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Folded

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