Exploration of the Powerhouse: Working Towards a Deeper Understanding of...

Exploration of the Powerhouse: Working Towards a Deeper Understanding of Mitochondria Function Hope College 4.95K subscribers Subscribe Like Share Download Clip Save 462 views Apr 21, 2022 Dr. Kristin Dittenhafer-Reed (Chemistry) Exploration of the Powerhouse: Working Towards a Deeper Understanding of Mitochondria Function Mitochondria, often referred to as the powerhouse of the cell, are essential for cellular energy production and proper cell function. My interest in understanding mitochondrial function began as an undergraduate and evolved through my research career. I will describe ongoing projects in my lab focused on understanding the molecular mechanisms that act within the mitochondria to control energy production. I'll also discuss my own understanding of my work as vocational Christian scholarship and discuss the important role that mentoring students plays in this work. * * To sign up for an in-person tour, visit https://hope.edu/admissions/visit/ To learn more about our academics, check out https://hope.edu/academics/ Follow Hope College on Instagram / hopecollege Key moments View all Transcript Follow along using the transcript. Show transcript Transcript Search in video 0:10 perfect thank you andy and thanks to both andy and lindsay for their leadership of the continuum 0:16 scholars program this summer as well as all of the other faculty who played a part in this as the 0:22 continuum scholars it was great we had really fruitful conversations and time 0:27 to reflect on things that i hadn't before during my time at hope at least not with others 0:32 so i will be talking a little bit today about my work with the mitochondria i love this image that's on the slide 0:39 right here all the green lines there are mitochondria within a cell and they kind of form this like energetic life force 0:45 that we'll talk about a little bit more as we go on so today what i hope to talk about uh 0:52 what are the mitochondria and why am i excited about studying mitochondrial function so i'll give you a little taste 0:59 of that then i'll tell a short snippet of ongoing research in my lab that's 1:05 focused on the regulation of mitochondrial dna transcription and then finally 1:10 end with a discussion of my faith and my scholarship so first what are mitochondria and so as 1:18 we've already covered mitochondria are the powerhouse of the cell and so again from kind of any introductory biology 1:25 class even as far back as probably middle school we learn about the different compartments of a cell and i 1:31 can remember like putting cell models together and putting little pieces in parts with styrofoam or something 1:36 and i always kind of love the mitochondria we think of it as this little bean shaped thing that you see on that mug 1:42 remember this mug i'm going to talk about this mug later in the talk but we'll go from there 1:48 so what are mitochondria we can also answer this question star wars has a great uh answer to what 1:54 our mitochondria so i'm going to show a quick clip here that will help us to understand what mitochondria are 2:03 master what are midichlorians midichlorians are a microscopic life 2:09 form that resides within all living cells they live inside me inside yourselves 2:15 yes and we are symbians with them symbionts life forms living together for 2:22 mutual advantage without the midichlorians life could not exist and we would have no knowledge of 2:28 the force they continually speak to us telling us the will of the force 2:35 the force the force is what gives the jedi is power 2:40 it's an energy field created by all living things it surrounds us midi chlorians are a 2:46 microscopic but this is going to be a problem if this keeps happening so let's see here 2:55 is that better okay maybe it was just twisted a little bit okay so the quote there is midi 3:01 chlorians are a microscopic life form that reside inside of our living cells without the midichlorians life could not 3:07 exist and they also explain the force okay so that's all i have to say today that's why i study mitochondria um 3:14 no i'm joking right so this is a funny little clip that i'm not the only mitochondrial biochemist or biologist 3:19 who likes to show this thing it's kind of a joke but there's a lot of things that are kind of true in here right like 3:24 life couldn't exist without mitochondria they are sort of a microscopic life form that reside inside our cells 3:31 through this process of symbiosis and so i'm going to hit on all of those things as we go forward um but let's dig in a 3:38 little bit deeper what are the mitochondria so the powerhouse what does that mean that mitochondria are the 3:44 powerhouse of the cell what mitochondria are required to generate most of the this molecule called adenosine 3:50 triphosphate or atp we'll ignore the chemical structure and just focus kind of on these three circles which are the 3:56 phosphates of that molecule and we can think of atp as running around the cell as like a charged 4:02 battery and it helps reactions occur that normally energetically wouldn't be 4:08 favorable so the hydrolysis of adp atp or the breakdown to adp now we have two 4:15 phosphates here is often coupled with a large number of different metabolic reactions that again could not occur 4:22 unless we use atp with it now where did the mitochondria come back in will the mitochondria come in in that 4:29 they regenerate this atp so they take the dead battery adp that's not really 4:34 useful for anything and they synthesize a ton of atp and so without this a number of 4:42 metabolic reactions couldn't happen life as we know it in our cells couldn't occur because we wouldn't have atp 4:49 and we need the mitochondria to generate this energy currency which is why they're known as the powerhouse of the 4:55 cell just some fun facts here about 110 pounds of atp are converted to 5:02 adp daily this is a ton right that doesn't mean 110 pound person is all atp 5:08 what's happening here is that each atp equivalent is recycled more than 500 5:14 times each day okay so the mitochondria have to be there to recycle adp to atp 5:21 and this process is occurring rapidly and all of the time and so that's why 5:26 the mitochondria get uh their name as the powerhouse of itself 5:33 there's some other fun facts about the mitochondria if i haven't sold you on them yet with star wars in the powerhouse 5:38 there are 10 million billion mitochondria in a human that is approximately 5:45 10 of our body weight mitochondrial proteins i'm a protein biochemist i get excited about studying 5:52 the machines of our cells the proteins within our cells that do kind of all of this work that we 5:58 need them to do account for about seven to ten percent of the entire human proteome 6:04 and then finally uh the mitochondria are central to metabolism of all sorts of dietary fuels so the mitochondria don't 6:12 just make atp they do a whole ton of other things beyond even just these 6:18 beyond just metabolism and when i think about my interest in the mitochondria and how i got to studying the 6:24 mitochondria i think it begins with metabolism and this interest in metabolism i remember being a kid and 6:30 and really being interested in maps and puzzles and logic and how does this all work together and when we think about 6:37 metabolism so this is a metabolic map but it's not intended for you to be able to read the pieces but just that you can 6:43 see right all of these different chemical conversions so each kind of line here is some chemical reaction 6:49 that's occurring within our cell that's involved in metabolism and i think it's beautiful that all of 6:55 these things happen in our cells it's regulated it's complex and trying 7:00 to understand how all of this works together is something that really interests me and the mitochondria which 7:06 if we look just kind of at this dark gray box all of these metabolic reactions are occurring within the mitochondria they're really central hubs 7:13 to cellular metabolism additionally another reason why i'm 7:20 excited about the mitochondria is this idea about their importance in human health and disease i think i've heard a 7:27 number of colleagues share a similar story that they entered into undergrad thinking that they were going to go into 7:32 medical school they were interested in science and they wanted to help people and med school was the way that you would do that and i was there i was 7:39 there probably until the end of my junior year i was pretty convinced i was going to med school 7:44 and some things happened i said oh no that's not what i want to do and so i i transitioned into realizing 7:52 you could use science as a researcher to also impact human health and understand human 7:58 disease so again i used to say to students tell me a disease and i'll tell you how the 8:03 mitochondria is implicated now that's hubris right it's overstatement but there's a little bit of truth that as 8:10 mitochondria began to fail we see these types of things in aging if we think of them as engines and as your engine 8:16 becomes less efficient right you release heat that's bad for a car similarly that's bad for a person as we get less 8:23 efficient mitochondrial function so mitochondrial dysfunction has been implicated in diseases like cancer 8:29 neurodegenerative disorders specific genetic kind of mutations within the 8:34 mitochondrial genome that i'll talk about that then cause disease and so 8:41 metabolism gets me excited about the mitochondria and their roles in disease also gets me excited about the 8:46 mitochondria so the goal of my lab at hope is to understand basic biochemistry of 8:52 mitochondrial function in order to enable a deeper understanding of mitochondrial dysfunction that occurs in 8:58 human disease so we don't come at it from a disease perspective i don't say our lab studies cancer i say our lab 9:04 wants to understand better how the mitochondria work in hopes that someone else might be able to use that 9:10 information in the context of a human disease and everything that we do is focused on 9:17 the mitochondrial genome or mitochondrial dna which is shown in this picture so again we see our 9:23 little bean of a mitochondria and within each mitochondria there are number of copies of mitochondrial dna 9:30 and where you might be most familiar with mitochondrial dna is through lineage tracing because it's thought to be maternally inherited and so some 9:37 people can you so you can trace mitochondrial dna throughout kind of um 9:44 maternal lineage lineages perhaps even to some mitochondrial eve shall we say 9:50 but i'm excited about mitochondrial dna for for some other reasons that i'll tell you about so mitochondrial dna again the small 9:57 circular genome recall we have genetic information now in two places in the mitochondria as well as in the nucleus 10:03 right where we think of the bulk of our dna before i get too far i know that this 10:09 audience we have people from all different places so i want to go through some words that i'm going to use and 10:14 make sure we all have the same kind of background so a central dogma of biology 10:20 we start with dna so either mitochondrial dna or dna in our nucleus we can think of this dna as like the 10:27 blueprint to an entire house through the process of transcription that's a word i'll use a lot in this 10:33 talk because we study transcription through the process of transcription we make what are called messenger rnas or 10:39 mrnas so that's like saying hey we want to build the door of the house 10:44 we don't need all of the instructions in the dna we just need the instructions for the door only so we pull the 10:50 instructions from the door only and make a message of that through the process of translation we go 10:57 from mrna and we synthesize our proteins so much like we could take the blueprint 11:02 for the door and then we could build the door okay so that's kind of these words that i'll use and talk about 11:11 so what do we study in the lab what what are we thinking about so we start up here with a mammalian cell 11:17 nucleus and mitochondria of course there are other bits and pieces of that cell but we're focused right now on just the 11:23 nucleus and the mitochondria and your cell could be likened to a city where all these different parts have to work 11:29 together in order for appropriate function to occur 11:34 let's focus first on the mitochondrial genome the mitochondrial genome codes just for 13 proteins and those 13 11:41 proteins are required for cellular energy production much like a power plant would be required for energy 11:48 production and distribution in a city now if we compare that to the nuclear 11:54 genome the nuclear genome carries the genetic information for over 20 000 proteins so this is orders of magnitude 12:00 greater when we compare the mitochondrial genome to the nuclear genome and this directs cell function 12:07 right much like city hall directs the city function city hall might be governed by a city 12:12 council the nuclear genome is controlled by transcription factors among many other things 12:19 now what i find most interesting when we think about the nuclear genome in the mitochondrial genome 12:25 is that there are a large number of proteins 1500 to 2000 proteins of which 12:31 the genetic information is carried within the nucleus but those proteins must be transcribed and translated into 12:37 proteins and then shipped into the mitochondria in order for them to to carry out their function 12:44 some of these proteins include transcription factors for mitochondrial dna so these things that control 12:51 the transcription dna to mrna also the protein machinery that's 12:56 required for transcription of mitochondrial dna so without the nucleus the mitochondria 13:02 cannot transcribe its own mitochondrial dna it's useless the mitochondria dna is 13:07 useless inside of the mitochondria unless the nucleus is there to help it and i think that that's really 13:13 interesting and then finally we talked about the powerhouse and the synthesis of atp 13:19 so there's 90 protein puzzle pieces that are required in order to generate atp directly 13:25 13 of those are encoded by the mitochondrial genome the remainder are encoded by the nuclear 13:31 genome so the mitochondria on its own cannot even make atp it relies on other 13:37 protein subunits that are that the information is carried in the nuclear dna in order for that to work 13:44 so this sets up a situation where these two genomes must communicate with each other in order to match kind of 13:50 energetic needs the cell says hey i need more atp the mitochondria can't go off and do its own thing without kind of the 13:57 nucleus being there to potentially help as well so the big questions in my lab 14:03 are how do the mitochondria nucleus communicate to connor to coordinate their transcriptional response to 14:09 changes in cellular energy demands so again if this idea we need more energy we need more atp kind of long term well 14:17 we need to boost the transcriptional machinery potentially which requires a nucleus we might need to boost 14:24 the number of components of the energy production machinery again relying on the nucleus how are these signals 14:30 relayed between the two compartments of the cell that's the big picture question that kind of drives my research and my 14:37 interest the second question is how is mitochondrial dna transcription 14:43 regulated in human cells and the third question which kind of is 14:48 tries to address questions one and two are that a number of proteins about 60 are known to associate with 14:54 mitochondrial dna but their roles in transcription and transcriptional regulation are unknown so my hope during 15:01 my career is to take a stab maybe not at all 60 but to start 15:06 plugging away at these proteins known to associate with mitochondrial dna and say are they doing anything important 15:13 in both protecting potentially the genome or regulating transcription of the genome 15:21 so what's our hypothesis what are we studying in the lab directly so our hypothesis is that things called protein 15:28 post-translational modifications regulate mitochondrial dna transcription so i presented this 15:34 this just to you a few slides ago the central dogma there's another layer of complexity on top of that central dogma 15:40 and those are these things called post-translational modifications where we can decorate the amino acids the 15:47 chemicals that are linked together in order to form proteins we can decorate them with different chemical 15:52 modifications and that changes the function of that protein so for example we could add a mail slot 15:58 to the door or we could put windows on the door we could take the doorknob away right so we've changed the function by 16:04 changing the chemical makeup of that protein so what do these looks like look like i 16:10 got to show a few structures here so one of the post-translational modifications we think about is phosphorylation 16:16 so phosphorylation occurs on hydroxyl groups or alcohol groups on three 16:22 different amino acids within our proteins and we can see chemically right that this is different so we've gone 16:28 from neutral to negative charge bigger kind of molecule on there so we can envision how sticking that in 16:35 potentially to a protein that binds to mitochondrial dna we've now stuck this negative charge in there and made it a 16:41 little bigger that could disrupt some interaction or cause an impact importantly these are reversible which 16:47 is kind of cool right so a protein puts this modification on a protein can take it off so it can act like a switch an on 16:54 off switch for protein function another modification that we think about is this modification called acetylation 17:02 and so again we're focused on the change that occurs to this nh3 group it's often positively 17:09 charged we've lost this pot of positive charge and again kind of changed the structure of that amino acid 17:18 it turns out that mitochondrial proteins have a ton of amino acids that are modified by these different types of 17:24 chemical groups so about 2500 acetylated lysine so a lysine is the amino acid and 17:30 i'll use the word site to refer to these modified places on proteins a 17:36 thousand phosphorylation sites and they're involved in all sorts of different processes within the 17:41 mitochondria and so my work back in grad school kind of started with trying to explore these different modification 17:47 sites that really kind of launched me into this interest in mitochondrial dna because i saw lots of modifications on 17:54 proteins that were involved in mitochondrial dna transcription and maintenance 18:01 further about 5 maybe less have a characterized biochemical function and so while we're 18:07 really interested in the lab and understanding mitochondrial dna transcription this is also helping to understand kind 18:14 of the bigger picture of why are these modifications within the mito mitochondria 18:22 so i'll tell you about three of our favorite proteins that we're focused on so this is a protein crystal structure 18:28 i think they're quite beautiful i like to look at them another reason why i like protein biochemistry uh what we're 18:34 looking at here in the orange and the blue and the green that's dna and these three proteins pull rmt which 18:41 is the polymerase it's the enzyme that actually synthesizes the mrna 18:47 in yellow here we see a transcription factor this transcription factor is important to get the polymerase at the 18:54 right spot on the mitochondrial dna and then the red protein here is tfb2m 18:59 or transcription factor b2 and it's super important and again kind of this appropriate alignment as well as 19:06 opening the dna up that's what promoter melting means we have to open the dna up in order for the polymerase to get in 19:12 there and start doing its job so a lot of our work is focused on 19:18 tfb2m although each of these proteins have documented 19:23 modification sites and this is either from literature from some work that we've done in the lab with the mass 19:29 spectrometer that we have that can kind of identify where on the protein these modifications exist 19:37 if you look closely you see kind of these space filling balls on tfb2m those are three modification sites that we've 19:43 studied and sought to understand their function i'm going to change colors here a little 19:48 bit i like this image a little bit better in order to see these sites but s197 that means serine 197 so one of 19:56 those amino acids in that protein which is known to be phosphorylated and then we have threonine 313 and 20:03 threonine 184 so three amino acids all known to be phosphorylated nobody knew 20:08 what they were doing if they played any important role in protein function 20:14 this s197 we looked at so i often have students look at these pictures and i say make a hypothesis 20:20 tell me what you think could be going on if the chemical structure of that amino acid changes 20:26 and so this really great kind of thing to look at and kind of investigative work we can do before even doing any wet 20:32 lab experiments in the lab so how do we study this 20:38 what we do is we use e coli we trick e coli into becoming little protein synthesis machines so much like an 20:46 organic chemist can synthesize an organic molecule and purify it we can have e coli synthesize a big organic 20:53 molecule a big protein and we can purify it away that's great but we have to somehow 21:00 mimic this phosphorylated group so here's just one example here we see the amino acid serine with it in its 21:06 phosphorylated form unfortunately we can't easily just make a protein 21:12 in the lab that's phosphorylated at a single site so we can't do that we have to mimic that phosphorylation in some 21:19 other way so we can mimic it by changing the amino acid at the position to either 21:25 an aspartate or a glutamic acid and you can see now that those 21:30 kind of look a little more similar than just an oh group okay and so we use 21:36 these what we call modification mimics to purify libraries of proteins that are 21:44 modified and then we go ahead and we study those in a couple of different ways so once we purify our proteins of 21:50 interest we can look at transcription inside of a test tube so we can actually say how well does this protein 21:57 transcribe dna and we can also assess its ability to bind to mitochondrial dna 22:03 with the idea that if it can't bind to dna it probably can't do its job in transcription as well 22:11 and so what we found from this work when we made these phosphorylation mimics of this protein is that when tf2m was 22:19 phosphorylated it didn't bind to mitochondrial dna as well and we've got a loss of mitochondrial dna 22:25 transcription so we pull tfb2m away and we no longer can transcribe dna 22:32 i have one data slide so this is it so i'm going to show you so you got to bear with me okay um so here's here's just 22:38 some of the data that support that picture that i showed you on the last slide so we have a template of a dna we give 22:46 it some mitochondrial dna in a test tube we give the system mitochondrial dna we give it our tfb2m protein the polymerase 22:53 and we say are you doing transcription or are you not doing transcription and so we can do these experiments we'll 23:00 just focus here on some of the things i have in boxes so what this is called is called a 23:05 runoff experiment and so that means can the polymerase start at the initiation 23:11 site for transcription and can it run off the template that we give it and so if we see dark dots it means yes 23:18 indeed it did run off and so for example wild type wt here we see two dark dots 23:24 um that means it did really well for serine 197 we see two dark dots that 23:29 means it did really well for these two other mutants phosphorylation mimics we see no dots right so it didn't do as 23:36 well um and so those are the data that kind of tell us that when we're looking at 23:41 t184e this phosphorylation site or the phosphorylation site at threonine 313 we 23:48 don't get productive transcription we can back up these claims 23:55 with some binding data so there's a lot going on here i'm not going to talk about it all i want you to focus on just a few things here so 24:02 if the protein doesn't bind to mitochondrial dna we would say that transcription likely will not occur and 24:08 indeed that's what we found in this study where transcription is not occurring and we 24:14 can look at how well each of the proteins binds to mitochondrial dna using a method called fluorescence 24:20 polarization the higher the number the worse the binding so we see high number here 455 24:26 nanomolar high number here compared to our wild type protein and so all of this kind of 24:31 nicely works together to say that we don't have binding and we don't have transcription 24:39 so what's next well what's next i showed you those other two kind of protein friends that are absolutely required for 24:44 transcription they have a bunch of modification sites we're kind of systematically working through those 24:49 proteins doing very similar experiments to what we showed here to say the core transcriptional machinery those three 24:55 proteins what are post-translational modifications doing what's next so mitochondrial dna again 25:03 binds to all these proteins right and i said i'd love to know what all 60 of these proteins are doing in 25:08 transcription so we know that there's proteins that are involved in packaging mitochondrial 25:13 dna they're called kind of nucleoid proteins it involves the core transcriptional 25:19 machinery which we're already studying and a number of really cool metabolic enzymes and so we're moving on we're not 25:26 moving on but moving into uh studying some metabolic enzymes as well 25:32 as we finish kind of understanding the transcriptional machinery the core transcriptional machinery 25:38 with the idea that these metabolic proteins are acting as sensors or rheostats of metabolic state and then 25:44 conferring that information to the mitochondrial genome to either enhance transcription or to decrease 25:50 transcription 26:00 okay i won't even touch it all right so that kind of ends uh that ends a little research portion we'll move on into the 26:07 third portion here maybe we will maybe we won't we'll see 26:13 i don't know if we have a bad hdmi or what 26:21 okay well it could be we're just going to leave it because it's working so so we're returning to the mug right okay 26:27 and andy kind of talked to you a little bit about this in the in the vocational biography that he uh presented at the beginning but i 26:34 entered the continuum program thinking man i really want to find this explicit connection between my faith and my 26:40 scholarship and i really wanted that i looked to lots of great people at hope doing research and can see kind of those 26:47 explicit connections and thought that's what it means to be a christian scholar there must be some explicit connection 26:52 that i haven't yet found for my work so i was frustrated the first two days of continuum because i'm like this isn't 26:58 helping i'm not finding anything and then we read something and a student 27:03 stopped by and gave me this mug with a nice little note and this student wasn't the best student 27:08 it was actually a student who took biochem one twice um with me so you i don't often think of getting 27:14 gifts from students who've had to take my class twice uh and this student the second time i was just a cheerleader i 27:21 wouldn't say that i went out of my way to do anything extra except to really acknowledge when they 27:26 were succeeding um and i think that that helped that student and the student did 27:32 fine and then ended up electing to take biochem 2 with me and so that really like spoke a lot and 27:38 then the student came back a year later and gave me this mug and told me they're off to a master's program 27:43 and stuff like that and kind of that along with some of the readings kind of came up at the same 27:49 time and i thought and maybe it doesn't have to be explicit and maybe through mentoring and the 27:54 relationships that i have with students and my colleagues i can demonstrate my faith in this way which is kind of 28:01 defined as purely vocational christian scholarship and so i think that through mentoring i 28:07 can really demonstrate my faith i can interact with people in ways that kind 28:13 of reveal to them things about my christianity and it's not always in 28:19 an explicit manner so again mentoring these are some of the awesome students i've had the privilege 28:26 of mentoring during my six years at hope in my lab these are the students that i 28:31 form the closest relationships with and get to have all sorts of interesting conversations with whether it's about 28:37 science or life or whatever and i feel very fortunate that these students are almost an extension 28:44 of my family and i still keep connected with my very first research student i was invited to her wedding in the fall 28:51 um and so those are types of relationships that i think being at a place like hope being a christian 28:56 scholar um a lot kind of afford these types of long-term connections 29:02 with students and i hope that through my mentoring i'm also kind of getting them to the places uh where they hope to be 29:10 so mentoring is certainly one aspect of of my vocation and my work as a 29:16 christian scholar but i do think that in the background i have questions 29:22 that um [Music] that kind of are related to origin of life questions and the mitochondria play 29:28 a very critical role in life right if we think back to the star wars video um 29:34 right they are kind of required for life as we know it and so i think as a 29:40 christian i'm very interested in this idea of both kind of science and faith and how they work together as and i 29:46 think that stems back to the origin of life right like where did this happen how did it happen um these 29:52 types of questions and so i'll talk a little more science here for a second so here we see an image of a 29:59 cell very very right early in evolutionary time some event occurred 30:06 in which a bacterial cell a proteobacterium was engulfed by some 30:12 sort of early eukaryotic cell so our cells are called eukaryotic cells human cells our eukaryotic cells 30:18 so this proteobacterium kind of was co-opted or engulfed by this early 30:24 eukaryotic cell and over the course of evolutionary time we get to the cellular 30:30 ancestor of kind of our cells without this event without kind of this symbiotic event of 30:38 the engulfment of this early mitochondrial precursor life as we know it probably would not exist right 30:45 because we need the atp that these things provide in order for the cell to continue to 30:51 grow and to become more complex et cetera et cetera and so i think in the back of my mind 30:57 this is really interesting and something that i like to think about even though i don't explicitly study 31:03 this connection and i'll just take this a little bit of step further to try to explain so again 31:09 at one point we had this ancient bacterial-like cell and over the course 31:14 of evolution we got to our mature mitochondria that we know of today 31:20 now over this evolutionary time scale lots of things happened and so some of the things that happened 31:26 was that information was transferred to the nucleus so at one point this was free living and it 31:33 did all the things that it needed to do on its own but i already emphasized the point to you today that the mitochondria 31:40 in our cells now cannot function independent of the nucleus it relies on this information within the nuclear 31:46 genome in order to function so these proteins that are encoded by 31:52 the nucleus and carried there but again throughout evolutionary time scales we're talking billions of years 31:59 it also the mitochondria also retained this small genome why 32:04 why did it want to retain this small genome and that to me is absolutely fascinating that the mitochondria has 32:11 this this genome that encodes only 13 proteins but it gave everything else up 32:16 to the nucleus if i knew how to study that i would but i don't but i think that that idea is kind of 32:23 really interesting and again brings in this perspective of faith and origin of life 32:28 that kind of drives an interest in the mitochondria and so i'll just end with a few quotes 32:33 the more i study nature the more i stand amazed at the work of the creator and so i hope that today i've given you a 32:39 little bit of a sense of that through my work and through my scholarship um i stand kind of amazed at that all of 32:46 this works how does it work right how does metabolism all work it's so complex 32:52 um how did this mitochondria come to be and why did these things get kept in the 32:57 mitochondria where other things got shipped away and so this is a quote by louis pasteur 33:03 which another kind of interesting connection here louis pasteur was one of the first scientists who 33:08 figured out that if there was oxygen around things grew better and so that's all about the mitochondria mitochondria 33:15 rely on oxygen to generate atp and i'll end just kind of with a few 33:20 more things about my thoughts on science and faith and so um there are people who are much more 33:26 articulate about this than i am and so i'm stealing from them for this presentation but someone so science and faith is 33:33 always this thing right and we can think about that when we think about origin questions we think about when we think 33:38 about evolution questions um and it seems like sometimes those things are at odds with each other 33:44 and i left probably undergrad thinking those two things were at odds with each other and i didn't know how to reconcile 33:50 it for myself i still don't but i'm kind of comfortable with that but i remember turning to some books and 33:57 one book that really helped me kind of put this put these pieces together about like i 34:03 can be a scientist and i can also be faithful francis collins you may know him he 34:09 just up until last month was the director of the nih he certainly has become much more in the public scene 34:15 with covid and things like that he was the leader of the human genome project the project that sequenced all of the 34:21 dna within a human and he writes in this book the god of the bible is also the god of the genome 34:26 he can be worshiped in the cathedral or in the laboratory his creation is majestic awesome intricate and beautiful 34:33 and it cannot be at war with itself and so i resonate uh strongly uh with this 34:39 kind of quote and just kind of stand in awe of what's happening in our cells at an atomic level 34:46 um he further says in another quote it's a miracle that it speaking of the universe has order fine-tuning that 34:53 allows the possibility of complexity and the laws that follow precise mathematical formulas contemplating this 34:58 an open-minded observer is almost forced to conclude that there must be a mind behind all of this 35:05 a profound truth that lies outside of scientific explanation and so i've used 35:10 the puzzle analogy already and for me i think there's lots of puzzle pieces that we as scientists can put together 35:16 they're probably always going to be like that piece that slid way under the couch or went down and you know my daughter 35:22 loses puzzle pieces all the time that we can't put the puzzle all together 35:28 and so to me that says there's something greater um that there's a greater mind behind all 35:34 of this that kind of has helped this to occur so with that i will end um and i'll just 35:40 say a quick acknowledgement um to all of my lab members folks listed there some collaborators 35:46 funding for the projects and then again to the continuum scholars program and to hope college for this experience 36:00 thank you kristen thank you for providing a presentation so wonderfully accessible to those of us 36:10 yes 36:22 um i will sometimes it works 36:33 you should be good 36:42 so i can understand that evolution works very well 36:47 on dna in the nucleus how does it work on dna in the mitochondria 36:55 if it's not doing the whole meiosis thing like it does in the nucleus or does it 37:01 does that question make sense i think so i i don't know i think so 37:07 so you're saying over time evolutionary time our dna has been altered within our 37:13 nucleus what happened in the mitochondria right because because i can if if 37:19 cellular information right in the dna moves to the nucleus then it there can use sexual and other 37:27 mechanisms to let evolution select on it and improve its function 37:34 does that same mechanism occur in the mitochondria is there meiosis and recombination there 37:42 no there aren't though i have never thought about that question that's a very interesting question no those types of things do not occur in the 37:48 mitochondrial genome um and i don't i don't know the answer to 37:54 your question so i i'll i'll try to answer it but it might not be perfect so that's what i'll say um and i don't know 38:01 a ton about this but so the mitochondrial genome again is inherited by the mom through maternally lin 38:06 through the maternal side and it's there are multiple copies of 38:12 mitochondrial dna within even a single mitochondria in development there's what's known as 38:18 the mitochondrial bottleneck where the amount of mitochondrial dna actually like kind of shrinks 38:24 um we'll go with that the amount of mitochondrial dna is 38:29 actually limited and then it's also just from the mom so we only want kind of the best mitochondrial dna to then go on 38:37 in the process of development and so that in some way kind of limits what 38:42 happens at least kind of in sexual reproduction about how the mitochondria are inherited 38:48 and things like that um but no the other events that you're talking about don't happen the mitochondrial dna 38:56 is kind of susceptible to damage that occurs within the mitochondria um but again we try to limit that with 39:02 limiting the amount of mitochondrial dna before kind of things take off that's the best i can do okay i think 39:09 that it certainly makes sense that with all the high energy stuff going on in the mitochondrion 39:15 you want to keep sensitive things outside thank you yeah 39:27 i have a much simpler question okay great but first let me thank you for your 39:32 presentation that clear metaphors were uh really helpful to somebody like me my 39:37 name is dave and i'm in the psych department but long ago in the early 1960s i was a 39:42 chemistry major and i was a biology minor unfortunately i've forgotten most of what i learned although i've stayed with 39:49 me what i've learned is my scientific empirical orientation to life but i don't recall learning about mitochondria 39:56 when did we come to appreciate mitochondria and their importance my goodness 40:02 that's definitely not an easier question i should know the answer to that but i don't know early 1900s i'm looking at leah i don't 40:10 know do you know yeah i don't know how long ago were you in school dave 40:16 i would definitely say people knew about the mitochondria before then 40:26 70s yeah yeah i mean i think the a lot of details 40:31 probably about the mitochondria i'm going to say 60 to 70s is like the um thinking about electron transport chain 40:38 and atp synthesis like those details um but linus pauline is certainly way before that and he kind of was one of 40:44 the first to start to think about these things but yeah that's a good question i don't know those states 40:52 yeah jason 1857 okay 41:03 thanks chris that was really great um my question will belie my biological ignorance because i was even younger 41:09 than david it wasn't longer ago but i was younger i was 13 the last time i had any of this kind of content um 41:15 are there still eukaryotes that don't have mitochondria or like we like that 41:20 it was you know once we have mitochondria all eukaryotes now have them yes correct 41:26 that event occurred early enough in evolution that you know fungi so having them wins out 41:32 over not having them yes 41:42 thank you okay so you said way long ago 41:47 a bacteria was like engulfed by the cell which is now the mitochondria but now 41:52 the mitochondria is like interdependent with the nucleus in order to do anything how much has like the 41:58 mitochondria really changed then like throughout that evolution to the point where now it almost like relies on the 42:04 nucleus to be able to do what it once did on its own yeah that's a really great question and and i don't again i 42:09 don't have a great answer that question because i don't think anyone really knows like what that early proteobacterium 42:16 exactly was maybe people know more than what i'm saying but certainly lots of genetic 42:23 information changed lots of regulation change right the mitochondria actually have probably developed more functions 42:30 than what they had when they were kind of on their own um we're you know we're talking 42:35 billions of years here of things that can happen and occur um so i don't know the explicit you know this pathway now 42:42 the mitochondria has and it didn't but i would envision that there's a lot of things happening with them 42:47 within the mitochondria that didn't happen just in that bug i would say that bug probably made a lot 42:53 of atp right and and then things kind of went from there 43:03 i have a question about i know you study how mitochondrial work and not how they don't work um but i know that in dance 43:10 marathon coming up in a month or so we've got at least one maybe more kids that have a mitochondrial dysfunction 43:16 which means sometimes it doesn't work out right and i'm thinking i know very little 43:21 again ignorance i'm laura i have no academic affiliation i'm staff so i'm 43:27 very ignorant on all of this but how does um if it is coming only from the mother and 43:34 i think of recessive and um genetic traits and you know the very basics that you learn 43:40 in middle school how does a mitochondrial disorder appear is it a 43:47 new mutation within the mitochondrial dna or is it is it how the mitochondrial interact with something else do you know 43:54 anything about disease causing mitochondrial dysfunction yeah so most of the diseases that children are 44:00 afflicted by that we're probably thinking about in this case not in the context of a thing like a cancer a 44:05 neurodegenerative disorder which is kind of a long-term decline in mitochondrial function those 44:10 disorders are oftenly often point mutations single nucleotide mutations 44:16 within the mitochondrial dna that then impact energy production so commonly 44:21 children will have kind of brain issues issues in tissues that use a lot of energy brain heart skeletal muscle 44:29 we see issues with children it you know comes out in children so those mutations can be inherited 44:36 through the mom um or they can be kind of mutations that occur sporadically all 44:42 mutations are random so a random event that occurs and it's in a really bad spot right in that really bad spot then 44:49 causes the disease but it can it can be inherited now there are other diseases 44:54 that are caused by the other things that you mentioned there but the ones that we see in children are how i just explained 45:01 i i have a question and that is maybe kind of tagging off of this what what are the implications of trans 45:08 mitochondrial transcription research going forward in other words as you do this research is it simply to advance 45:15 the biological science are there other implications for disease or yeah that 45:20 kind of thing as you do this research yeah that's a really great question so um 45:25 i think my goal really is let's understand how the mitochondria function better right 45:31 we don't know these pieces of the puzzle let's try to understand them and through understanding the transcription perhaps we can then 45:38 understand further how the cell works right a bigger question of biology 45:44 there are some human disorders that are caused by defective mitochondrial dna 45:49 transcription um kind of just these random energy issues uh 45:54 we looked at a paper this summer with the mitochondrial polymerase having some mutations and issues that led to its 46:01 dysfunction and so there are some one-off cases where we see these types of things in human disease 46:07 and so there are implications there but really our route is to try to understand 46:13 basic biochemistry that helps us understand how a cell functions 46:20 oh one more here can i yes let me let me 46:27 thanks i don't i don't really have a question i just wanted to comment i appreciated your um discussion of how you combine your 46:34 faith with your teaching so i'm not a biochemist but i do teach a a class to 46:39 kinesiology students who don't have a lot of chemistry it's called regulation of human 46:45 metabolism and we learn about all of the pathways and how we're able to provide atp 46:51 for sprinting compared to you know prolonged exercise and and one of the ways that i try to 46:58 um combine my faith with the concepts that we talk about is all the intricate ways that the 47:05 different enzymes and the pathways work together and and ask the students constantly you know why does it make 47:11 sense that it works this way to allow this pathway to work whereas that pathway doesn't work when this one is 47:17 working and i think the students um appreciate that so i 47:22 we don't go into any of the details um with structures or or 47:27 really bonding or anything with the students but i think just thinking of the big picture of how 47:35 god designed our bodies to work the way they do it is a nice way to do it so um and then 47:42 dave i think um when i teach about this it was 1967 that the mitochondria the we 47:48 learned about the electrochemical gradient and how that allows oxygen to be used so maybe that's why 47:55 you didn't learn that so much in the 60s anyways 48:00 thank you dr meyer would you like to have the last question here 48:07 it's kind of a stupid naive question but is there a boundary between biochemistry and microbiology and if so what is it 48:14 and which side of that boundary are you on yeah i think we i think as scientists we start to use 48:20 these terms a little bit loosely but i my definition would be a microbiologist studies 48:26 bacteria and yeast um and things like that whereas as a 48:31 biochemist where biochemistry is probably the biggest umbrella where people take that into different places but as a biochemist one might be a 48:38 protein biochemist like what i am i study protein function molecular interactions functions of molecules 48:44 within our cells those types of things so that's how i would loosely define those two things 48:51 well i want to tell uh you again christian thank you for a fantastic lecture today it was a delight 48:58 to have you be a part of our group this summer i your your thoughtful reflection here on your 49:03 own scholarship your faith was characteristic of conversations we had this summer and i just really appreciate 49:10 the time with you and you sharing with us today can we thank doctor didn't help from read again please thank you Hope College 4.95K subscribers Videos About Instagram Facebook TikTok LinkedIn 0 Comments rongmaw lin Add a comment...