Ming Hammond is Asst. Professor of Chemistry, Molecular & Cell Biology. Her research combines Chemical and Molecular Biology, Organic Chemistry; Reengineering functional RNAs, and mechanistic studies of RNA-based gene regulation. She created the web site youstem.org.
Transcript
Speaker 1: Spectrum's next.
Speaker 2: Okay.
Speaker 1: Welcome to spectrum the science and technology show on k a l x Berkeley, a biweekly [00:00:30] 30 minute program bringing you interviews featuring bay area scientists and technologists as well as a calendar of local events and news.
Speaker 3: Good afternoon. My name is Brad swift and I'm your host. Our interview is with assistant professor of chemistry and molecular and cell biology Ming Hammond. Her research combines the fields of chemical biology, organic chemistry, molecular biology and bioinformatics. Ming Hammond [00:01:00] received her bachelor of Science Degree from the California Institute of Technology and her phd from UC Berkeley. She created and maintains the website you stem.org this site consolidates opportunities in science, technology, engineering and math for primary and secondary school students in the Greater Bay area. Assistant Professor Ming Hammond. Welcome to spectrum. Hello. Thank you. Would you give us an overview of [00:01:30] the research that you're doing and in so doing, remind us what DNA and RNA are and how they're different.
Speaker 1: Okay. Okay. I think a analogy that I like to use to describe the difference between DNA and RNA is that you can think of DNA as kind of an instruction manual for life. So that a very large instruction manual, several billion letters in length and it has all the instructions for how to make [00:02:00] all of the molecules, all the functioning parts of the cell RNA are messenger RNA is, are basically xerox copies of some pages of the DNA instruction manual that, um, gets used by the cell to translate the instructions into making proteins like enzymes and other components of the cell. Um, my lab is interested in how these RNA sequences are [00:02:30] regulated, how they're sent to different places in the cell and also how to change them so that we have, maybe we can control how the instructions are being used by the cell.
Speaker 3: And so with that research, are you trying to create a generally applicable way to alter the RNA so that the gene is expressed differently?
Speaker 1: Um, yes, exactly. And [00:03:00] first of all, understanding in nature how natural systems, um, control gene expression. And one reason we're interested in this is because for multicellular organisms like humans or plants, you have the same instruction manual in every single cell and yet you have multicellularity, right? So you have differences, different sets and instructions are being expressed [00:03:30] in different cell types, in different organs and in different portions of plants. For example, and were interested in understanding the basic mechanism for how the Messenger RNA is involved in ensuring that specific instructions are being followed in specific tissue types or specific cell types.
Speaker 3: Does that then also include the idea that you mentioned of [00:04:00] certain of the messages are incorrect on purpose and so understanding that sounds complex,
Speaker 1: right? So it's kind of interesting that one of the ways in which you can control, for example, whether a specific gene is expressed in the heart versus in the liver or the brain for example, is that messenger RNA for the same gene in the [00:04:30] brain is correct and can give rise to the proper protein and in the heart the same gene set of instructions can be spliced into messenger RNA in this specific way. That gives you a slightly different form of the protein. For example, one that has a slightly different function and therefore specific for that tissue. And then in the other case that I described, you might find in yet another tissue type that the same [00:05:00] message can be spliced so that it actually has a signal that says this is a garbage sequence, this is a nonsense message, don't follow this message. And the sal is smart enough to read these nonsense messages and know them to be nonsense. And what they do is the cell actually degrades these RNA. So for example, in that specific tissue type that the protein is never made. And so that's how you get [00:05:30] specialization of self.
Speaker 3: And in your research are you trying to understand all of those cases?
Speaker 1: We do most of our work in plants and we're very interested in the case where you can effectively shut off Accion in one condition, in war one cell type versus having it on or expressed in another cell type. So in plants, the mechanism that we study is [00:06:00] how these messages are lysed in these different ways. And that's called alternative splicing. And the predominant function of alternative spicing and plants appears to be this latter case where the messages either made and it's correct or it's made and has nonsense, but the reason I mentioned the other case is that it turns out something that's differentiates humans, for example, or mammals from plants. Besides the obvious differences, but a subtle [00:06:30] difference. The one I'm interested in is it turns out the majority of alternative splicing in mammals is actually to make different forms of that protein, so it's kind of interesting how the same basic mechanism is used by different organisms to do different things.
Speaker 4: [inaudible]
Speaker 3: you were listening to spectrum on k a l x Berkeley. Today we're talking with assistant professor Ming Hammond about [00:07:00] her work in messenger RNA and gene expression
Speaker 4: [inaudible]
Speaker 3: does the nonsense message have some value that you are researching that you are interested in understanding what is, what is the value of it to the, to the organism.
Speaker 1: Okay. It's very important for the organism in general that the cell needs to have a way to know when a message or when a messenger RNA is [00:07:30] instructing nonsense because it's actually known that you can have mutations, for example, if you have a mutation in your gene that gives you a bad message. If sometimes that message then gets expressed as a protein, that protein with this altered function or ane may in fact lead to detrimental results, bad results for the south. Right. Um, and so, um, in general, the, there's a, [00:08:00] we call it a surveillance mechanism, so the cell is actually looking out for dad copies of the Messenger RNA. And so the cell normally has these surveillance mechanisms to, to, to play a very important role in keeping the, and keeping the cell healthy. And so I think what has happened is that the cell has started exploiting this mechanism to regulate chains for [00:08:30] tissue specificity and all of these other things I mentioned
Speaker 3: in this regard. Are some cells smarter than others?
Speaker 1: Hmm. I, I wouldn't say that [inaudible]
Speaker 3: in terms of evolutionary activity, it would seem that this is kind of the place where that might go on in terms of changing an organism over time. How would RNA and nonsense allow for some sort of an evolutionary capacity to happen?
Speaker 1: Okay. [00:09:00] First of all, the surveillance mechanism does not change the genomic DNA or she does not change the DNA instruction manual.
Speaker 3: It's too far down the pipeline, right? So it's just reacting to the DNA instruction set, right? So it's really not there that any evolutionary activity is going to happen. It's going to happen at the higher lows. Right?
Speaker 1: There are people that look to see for example, which, uh, which organisms do have this mechanism, right? So it's not that [00:09:30] some cells are smarter than others, but more that there are some organisms that don't have this surveillance pathway, for example. And bacteria do not, as far as we know, have NMD pathways, um, this nonsense mediated decay pathways, but a lot of organisms with a nucleus to have this mechanism. But one of the things that we're interested in in the lab is there is a lot of people that study this mechanism in humans and in other mammals. [00:10:00] And we're working in this in plants and we're looking at the comparison between them. What are the differences and what are the things that are similar
Speaker 3: in your research? I noticed that there's something called molecular sensing that you're interested in. Can you explain that?
Speaker 1: Sure. So, um, I mentioned that were studying how gene expression is regulated at the RNA level. And one of the really fascinating [00:10:30] things that I worked on as first as a postdoc and now that we're still working on in the lab is it turns out some of the Messenger RNA [inaudible] that exist in bacteria don't just encode the sequences for making proteins. But there is a little extra part of the Messenger RNA in the beginning part of the messenger RNA sequence that encodes what we call a ribo [00:11:00] switch. You can think about the riboswitch as basically a natural chemical sensor that's hooked up to the Messenger RNA. And what the rabis switch does is it responds to the presence of a chemical, for example, whether there is plenty of an amino acid in the south and the RNA is able to sense the presence of say the [00:11:30] amino acid and when it binds to this chemical, it changes its shape and through this confirmation or shape change, it causes the message downstream to actually get shut off. If you have enough of the amino acid, you turn off the gene that is used to make that amino acid because you don't need anymore. So I turns out there are many, many of these rabis switches [00:12:00] performing this simple chemical, boolean logic at the RNA level doing molecular sensing and in my lab were of course interested in the natural, these natural ones. And we're also interested in making unnatural ones as well.
Speaker 3: And how is it that you utilize that information?
Speaker 1: One way you can make use of the [inaudible] switch as I mentioned, is that its normal function is to turn on or turn off a chain depending on [00:12:30] the natural chemical logic is. So it turns out you can take the DNA sequence that encodes the ribo switch and you could put it in front of a different gene. And now that other gene also responds to this chemical. So it's actually a portable logic gate, so to speak. And what we're interested in is in making new Ribas switches, for example, making ones that can work in plants [00:13:00] because there is so far as we know, only one natural rubber switch that functions in plants and were interested in exploring whether we can transport these chemical sensors and utilize them and in other organisms including plant.
Speaker 5: This is spectrum. I'm k a l x Berkeley. We're talking with the assistant professor Ming Hammond [00:13:30] about her research with messenger RNA and how it interacts with DNA genes. [inaudible]
Speaker 3: so are you building those pre-IPO switches yourself or are you borrowing them from other organisms?
Speaker 1: Um, well I would say it's actually a mix of both. We are also fundamentally interested in the mechanics of it too, right? How, how riboswitch with dysfunction. What is really amazing about Rabis, which is [00:14:00] is that there are so many different species of bacteria that utilize these Ribas switches and these bacteria live in all different types of climates than of them can live in extreme temperatures, both hot and cold and others are more, you know, soil dwelling organisms and live at pretty close to room temperature and all of them have the same sensor. And it's kind of an interesting question to ask how it is that the same sensor works [00:14:30] in all of these organisms? What part of the sequence of the, the switch of the RNA is responsible for for that [inaudible].
Speaker 3: So largely you, you work from the gene DNA area down into the RNA to control the expression of that gene.
Speaker 1: Everything that we do does start the DNA level and we have in mind and designed for messenger RNA that we want. And then we can go back and say, okay, [00:15:00] at the DNA level, this is what the DNA instructions have to be to make that messenger RNA. And then we see, okay, let's build it weak. Then express it and see, okay, is the RNA doing? What we want it to and then further on is this messenger RNA being shut off the way that we want it to under this condition and then turned on under a different set of conditions.
Speaker 3: And how do you judge whether or not you've had success? Is it pretty black and white [00:15:30] or is it somewhat gray?
Speaker 1: One of the kind of very basic techniques that we use is a very simple assay. So you can imagine if we wanted to see whether under condition a this messenger RNA we designed is not making the protein versus condition B when when it is. So what we ended up using is what we call a reporter gene, a gene that expresses a protein that is fluorescent so that if [00:16:00] you shine light at a certain wavelength, you get a light emission from this protein. So we express the gene and in this case on the surface of the plant leaf and we can scan the leaf and let's say condition a is on the left hand side and condition B is on the right hand side. And we'll actually see that the right hand side, the leaf will be glowing and the left hand side of leaf not be glowing because of Ganar that we use to tact [00:16:30] the light emission from the surface of the leaf. Uh, it actually shows up as a gray scale limit. So that's how it turns out.
Speaker 3: The organisms that you're currently working with, how do you select them?
Speaker 1: One of the ways that you would want to select an organism is, is that other people have worked with the organism and that it's been shown by other researchers that it's easy to do the experiments that you're planning and that there are protocols developed for the experiments [00:17:00] that you're planning. And so it's kind of expedient, but we pick a plant called Nicole [inaudible], Tami Ana that is actually cousin to the tobacco plant, which is of some agricultural interests and also has been shown by other people to be very easy to work with for our experiments.
Speaker 3: How has the hardware and the software that you use to do your research changed over the past? What 10 years that you've been doing this [inaudible]
Speaker 1: [00:17:30] so we don't actually use much software. We can talk about the hardware. Sure we can like the development of technology to do DNA sequencing very, very rapidly has really been astonishing to see. And for my research in the RNA field, it has an equal impact I would say as well because it turns out if you want to study an RNA sequence, one of the ways we study it is that we do what's called a [00:18:00] reverse transcription. So we convert the RNA back to DNA and then we sequence the DNA that's made from the RNA. So it's kind of the reverse of the normal case of things that technology has enabled people to not just look at the human genome, but what we called a human transcriptome. So this is what are all the Messenger RNHS that are being expressed in different tissue types. And so that has led us to discovering, for [00:18:30] example, these differences in expression at different, um, messenger RNA is on a much, much grander scale. It much, much higher throughput scale than was possible 10 15 years ago. More fundamentally, it has made certain experiments that were impossible to do possible. Now the next challenge is how to sort through all that data
Speaker 6: [inaudible]
Speaker 5: you are tuned to k a l [00:19:00] x Berkeley. You're listening to spectrum. We're talking with Assistant Professor Mang Hammond about RNA based gene regulation
Speaker 6: [inaudible].
Speaker 1: Can you explain the a youth stem.org website and I believe you started this, didn't right. So my lab and I started this website called youth stem.org and the inspiration for the website is, it's actually kind of a personal story, [00:19:30] but I think it resonates with a lot of young scientists and other scientists is when I was a younger student, even before I went off to college and I was deciding what subjects I liked, what I like to do, I had these opportunities where yes, some of my science teachers saw something in me or thought that I would enjoy science and wanted to encourage me in the sciences and they would suggest that I go and do some of these programs that [00:20:00] are available in the state of Maryland, for example, where my family is from. And you know, I had a chance to work in a lab at the University of Maryland School of Pharmacy.
Speaker 1: And I remember that made a really big impression on me when I was a freshman in college. And my freshman advisor asked me what I wanted to do for work study. I said that, well of course I wanted to do research in a lab because I said why I was already in a lab and in high school and I really liked it [00:20:30] and that's what I want to do for work study. And it was really exciting and really fun. So that's the origin story I guess of you stem. And in fact we have a lot of programs on the Berkeley campus for students interested in science that are, and that some of which pay actually a stipend. And not everyone can afford to pay money to do a summer program, but we have these free programs [00:21:00] that are I think really great. So I wanted to have a mechanism to point that out to local area students.
Speaker 1: And the kind of idea I had was, well wouldn't it be great if we had like essentially a craigslist for bay area free local science and engineering and math programs? And so that's um, basically what we intend for a stem to be. [00:21:30] You can actually go on the website. It's you stem.org and you can click on a subject. You know, my favorite subject of course is chemistry. And so you could pick chemistry and it'll actually show you just the programs that are for students interested in chemistry. You can search by your grade and it tell you which programs are for you or you also filter by the location. So we're focused a lot on the East Bay, but there are also programs down in the South Bay down [00:22:00] in San Jose, Santa Cruz that we found in ones up in Monterrey.
Speaker 3: So for people locally within the bay area who do have programs, they could contact you through the web.
Speaker 1: Right? There's actually a link on the bottoms saying you're saying if you're a program director and you would like to list your program, the criteria is that we're interested in listing programs where the students can apply themselves or it can be nominated by a teacher that it's open to [00:22:30] any student that wants to apply. And uh, certainly we emphasize programs that are free or that pass state band.
Speaker 3: And you recently received the NIH director's new innovator award. How did that happen?
Speaker 1: Well, the short answer is I applied but um, yes. So it's, it's a really great honor to have received it and actually [00:23:00] to a members of the chemistry department received the new innovator where I this year, myself and Michelle Chang, another assistant professor in the same department. And so it, that was just really great news for both of us. And yeah, it was really a day for celebration in the lab for sure. I mean Hammon thanks very much for coming on spectrum. Thank you. It's a pleasure to be here. Thanks for having me. Brad.
Speaker 6: [inaudible]
Speaker 3: [00:23:30] irregular feature of spectrum is to mention a few of the science and technology events happening locally over the next few weeks. Rick Kaneski joins me for the calendar.
Speaker 7: Come to nerd night [00:24:00] on Wednesday, January 18th at the rickshaw stop, one 55 [inaudible] street at Venice in San Francisco, doors at seven 30 show at eight. All ages are welcome to this $8 show at this month and our night copies of the inaugural issue of nerd night magazine will be given away. There's an article in there about cephalopod sex by the bay area's own. Rich Ross, Robyn, sue Fisher and Corey bloom will share their stories of liquid nitrogen ice cream. Their company smitten in San Francisco's first [00:24:30] made to order scoop shop and they will show off the engineering marvel that is dubbed to Kelvin that can churn up ice cream in under a minute. What do you love? Bounty and David Gallagher. We'll present Carville by the sea. San Francisco's Streetcar, suburb, and you CSF, Phd Student Tsai. Dear Etsy, we'll talk about antibody engineering and how artificially created antibodies can or will eventually fight disease. Visit s F. Dot. [inaudible] dot com for more information,
Speaker 3: smoke [00:25:00] and mirrors is geoengineering a solution to global warming. Professor Alan Robock from the Department of Environmental Sciences at Rutgers University will address this question. Wednesday, January 25th 4:00 PM in Barrels Hall Room One 10 on the UC Berkeley campus. This event is free and open to the public
Speaker 7: on Thursday, January 26th from seven to 9:00 PM the bone room at 1573 Solano avenue in Berkeley or present [00:25:30] eye to compound eye, the art and science of insect photography. In this free lecture insect photographer Becky Jaffe will incorporate and it dotes from biology, ecology and cultural anthropology to offer an engaging account of her field experiences that will inspire you to pick up the camera and look at insects with new eyes. Visit www.boneroompresents.com for more information now a few news items. Here's the Rick science [00:26:00] news reviews. A January 5th article in science by Sandra Garrett and Joshua Rosenthal at the University of Puerto Rico Medical Sciences campus in San Juan that shows that while octopuses in the Arctic have very similar DNA with warm water octopuses, their nerve cells are very different. This difference allows them to operate in the frigid waters and arises due to m RNA edits. These edits change the way that nerve cells opening includes gates to produce electrical impulses based on the species of octopus. This is the first [00:26:30] discovered example of m RNA editing to help an organism adapt to its environment and speculation remains as to how quickly and prevalent the mechanism might be.
Speaker 3: In December, NASA announced seventh 2012 as the new target launch date for the space x commercial orbital transportation services milestone missions two and three. This mission begins with the liftoff of the Falcon nine rocket from Cape Canaveral boosting the Dragon's [00:27:00] spacecraft into low earth orbit. The space x dragon spacecraft will perform all of the commercial orbital transportation services, milestone mission two objectives, which include numerous operations in the vicinity of the International Space Station, and thereafter we'll perform the commercial orbital transportation services milestone mission three objectives. These include approach birthing with the International Space Station, astronauts opening the dragon spacecraft [00:27:30] and unloading cargo. Finally, the astronauts will close the space craft and send it back to Earth for recovery from the Pacific Ocean off the coast of California. This mission, if successful, will mark a major milestone in commercial American space flight
Speaker 7: did January 4th issue of the Journal of neuroscience has an article by UCLA is Jenn Lang and others that reports promising anti-alcohol effects of a seed extract from the Asian Havana Dakis or Japanese [00:28:00] raising tree. This was first claimed to be a hangover remedy in the year six five nine rats that took dihydro, Myostatin or [inaudible] were found to take longer to become intoxicated and recovered four times more quickly than rats who did not take the extract. The extract further decrease the likelihood of hangover, anxiety and seizures in the rats. DSM also curved alcohol consumption. Rats consumed more and more alcohol gradually when it allowed, but d h m leased alcohol does not lead to this increased [00:28:30] consumption. DHM blocks alcohol's effects on Gaba receptors and the team has found no side effects in animal testing. They old next study the health effects on people
Speaker 2: [inaudible]
Speaker 4: the music heard during the show is from a low stone, a David album titled Folk and Acoustic released under a creative Commons attribution license 3.0
Speaker 2: [00:29:00] [inaudible]
Speaker 4: production assistance from Rick Karnofsky
Speaker 2: [inaudible].
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