Carrie Poppy, Tech Times
Read the Article in Tech Times
Biologists want to manipulate your mouth to do something extraordinary: grow extra teeth. And they're getting their advice from fish.
In the developed world, we often take for granted just how important having healthy teeth is. But in cultures without widespread dental care and fluoridation, the situation can be dire. Worldwide, 30 percent of people will lose all of their teeth by the time they're 60. So while it might sound freaky to convince your jaw to make extra incisors, it could actually vastly improve many people's lives. And fish can already do it.
Much like stem cells in humans, certain fish have special cells in their mouth that are extremely flexible; they can form teeth or taste buds, depending on the animal's needs. As a result, cells that are laying dormant can be triggered and differentiated as soon as the fish loses a tooth. That's a lot more clever and adaptive of a system than what humans have: two sets of teeth and no wiggle room if you lose them.
"There appear to be developmental switches that will shift the fate of the common epithelial cells to either dental or sensory structures," said Todd Streelman, a professor in the Georgia Tech School of Biology, and coauthor of the study, in a press release. In other words, there appears to be an on/off switch inside every fish's mouth cells. Flip it, and the cell becomes a tooth, leave it, and it becomes a taste bud.
The Georgia Tech researchers, along with scientists from King's College London, are studying the embryos of fish called cichlids, who live in Lake Malawi, home to one of the most diverse fish populations in the world. There are over 1,000 cichlid species in the lake, alone. Because there are so many species of these fish in a relatively small area, they have varying adaptations that inform the development of their teeth. Some eat plankton, and only need a few teeth over their lifetimes. Others eat algae, which they have to scrape off of rocks like so much corn on the cob, ruining their teeth as they go. They have to develop new teeth all the time.
By comparing these species and checking out the differences in their DNA, the scientists were able to single out the mutations that make it possible to grow extra chompers. Now, the next step is to figure out how the same can be triggered in mammals. But they (probably) won't be actually engineering your grandkids to grow extra teeth.
"The more we understand the basic biology of natural processes, the more we can utilize this for developing the next generation of clinical therapeutics: in this case how to generate biological replacement teeth," explained Professor Paul Sharpe, a coauthor from King's College. That could come in the form of cell cultures, laboratory animals or, less likely, turning future generations into fishy freaks.
The study was published in the Proceedings of the National Academy of Sciences of the United States.
Dr. Chrissy Spencer was appointed an OER Research Fellow for 2015-2016. The William and Flora Hewlett Foundation sponsors OER Research Fellowships to do research on the impact of open educational resources on the cost of education, student success outcomes, patterns of usage of OER, and perceptions of OER. The OER Research Fellowships are competitive, and OER grants are administered and supported by the Open Education Group.
Emily Singer, Quanta Magazine
View the Artcile in Quanta Magazine
Until one or two billion years ago, life on Earth was limited to a soup of single-celled creatures. Then one fateful day, a lonely cell surrendered solitude for communal living. It developed a chance mutation that made its progeny stick together, eventually giving rise to the first multicellular life.
With that simple innovation, a world of possibilities burst open. These new organisms were too big to be eaten, and their mammoth size allowed them to pull in more food from the environment. Most important, individual cells within the bunch could begin to specialize, taking on new functions, such as hunting, eating and defense. The transition to multicellularity was so successful that it happened over and over again in Earth’s evolutionary history — at least 25 times, and very likely more.
Multicellularity has clear advantages — just look at the menagerie of form and function among animals, plants and fungi. But scientists have long been puzzled as to how this transformation took place. A true multicellular organism acts as a unit, meaning that each cell must surrender its will to survive as an individual and act to ensure the survival of the larger group. “The problem with all the major evolutionary transitions is how Darwinian entities relinquish their individual fitness and become part of a higher-level unit,” said Richard Michod, an evolutionary biologist at the University of Arizona in Tucson.
Scientists are gaining insight into the process by re-creating the evolution of multicellularity in the lab. Using an approach known as experimental evolution, they prod single-celled microbes, such as yeast, algae or bacteria, to develop a multicell form.
“It’s easy to think of [these major transitions] as a giant leap in evolution, and in some sense that’s true,” said Ben Kerr, a biologist at the University of Washington in Seattle and one of the researchers studying major transitions in evolution. But each transition actually involved a series of small advances — the organisms had to evolve effective ways to stick together, to cooperate, to divide and to develop specialized jobs within the greater whole. “We’re trying to do the opposite of a giant leap. We’re trying to break one giant leap for evolution into an understandable series of small steps.”
William Ratcliff, a biologist at the Georgia Institute of Technology in Atlanta, and his collaborators have discovered a surprisingly simple route to multicellularity: a single mutation in yeast that adheres the mother cell to its daughter to create a snowflake-like shape. These snowflakes grow and divide in a way that provides a clever solution to one of the major pitfalls of multicellularity: the cheater problem, in which lazy cells take advantage of cooperative ones. And while the work hasn’t produced a true multicellular organism, the snowflake yeast has shown just how easy it can be for life to take the first step toward a major biological transformation.
Ratcliff began his quest for multicellularity while still a graduate student at the University of Minnesota. Over a series of coffee-fueled conversations, Ratcliff and his collaborator Michael Travisano began brainstorming the “coolest experiment we could do,” according to Ratcliff. Tackling the biggest unsolved question in biology — how life first began — was too far out of their wheelhouse, the pair decided. So they settled on the runner-up: How did multicellular creatures evolve? To untangle that transition, the researchers would try to re-create it, converting single-celled yeast into multicellular organisms.
Ratcliff and Travisano developed an easy way to force yeast to become multicellular. They grew the microbes in tubes and spun them in a centrifuge once a day. The largest cells or those that clustered together sank the fastest. Each day, they selected the fastest sinkers, challenging those cells to another round of the experiment. Over the course of 24 hours — roughly seven generations of yeast — the cells accumulated tens of thousands of mutations.
Then, a couple of weeks into the experiment, the composition of a few of the tubes suddenly changed. The cells began forming large clusters, and the silky solution of single cells transformed into grainy blobs. Within 100 yeast generations — about two weeks — the population had shifted almost entirely to snowflake yeast.
“I was gobsmacked,” Ratcliff said. “It was unusual, fast and dramatic.” Peering at the solution under the microscope revealed that single cells were now in the minority. “We mostly saw these beautiful spherical branched things.”
While typical yeast divides and disperses after each generation, snowflake cells divide and stick. Daughter cells cling to their mother like baby kangaroos. Mother and daughters then divide again and again, each producing another attached offspring.
The evolution of snowflake yeast created more than a mere clump of cells. Wild yeast strains sometimes produce a sticky protein on their surface, which makes the cells adhere to each other. Brewers like this sticky form, known as floc yeast, because it’s easier to remove it from newly brewed beer.
But snowflake yeast is quite different from flocs. Floc yeast cells divide and separate, then condense into a genetically diverse pile. Snowflake yeast grows in highly related clumps. It’s this difference that Ratcliff and others say distinguishes a simple blob of cells from a cohesive unit capable of evolving true multicellularity.
Whether snowflake yeast qualifies as truly multicellular or not is a difficult question to answer. There’s no clear dividing line between single-celled and multicellular organisms. Ratcliff likens the transition to what he calls the rich man, poor man problem. If you gathered everyone in the United States and lined them up according to wealth, the richest people would land at one end and the poorest at the other. If you just looked at these extreme ends of the spectrum, it would be easy to define the characteristics of the rich and the poor. But if you drove down the line of people, it would be impossible to define a strict point where the rich group ended and the poor group began. By this analogy, snowflake yeast is in the multicellular middle class.
The Nature of Individuality
Around Christmas six years ago, Ratcliff slid a photo of his snowflake yeast under the door of a historian colleague who studies the nature of individuality and asked him to identify the individuals: Were they the single cells that made up the snowflakes, or the snowflakes themselves? The historian drew Santa hats on the snowflakes, a tongue-in-cheek method of choosing the multicellular entities.
Ratcliff was trying to get at the question of how to define an individual, one of those superficially simple questions that are actually quite complex. And while biologists don’t agree on the exact qualifications that designate an individual, they do have a broad set of guidelines. Snowflake yeast satisfies a number of important requirements.
First, individual cells within a snowflake appear to sacrifice themselves to benefit the whole. When snowflake yeast reaches a certain size, cells within the clump commit suicide, releasing smaller daughter clumps from the parent cluster. “It’s deeply poetic: The death of individual cells seems to be a direct contributor to the birth of new multicellular organisms,” Kerr said. The process illustrates the beginnings of a division of labor within the organism. Individual cells have distinct roles to play, even if their role is simply to die. “It’s not in the interest of the individual cell — it’s shifted interest to a higher level.”
Snowflake yeast also mirrors the genetic bottleneck that we all go through. Every one of us began as a single cell, a fertilized egg that produced the complex layers of tissue that make up our bodies. Each daughter branch in snowflake yeast is composed of cells that originated from the same parent cell. In both cases, the resulting block of cells is genetically identical, or nearly so.
That homogeneity is essential for blocking the spread of cheater cells, the single-celled equivalents of lazy roommates who eat everyone’s food but never go shopping or pay the bills. Cheater microbes steal resources from their neighbors and devote all their energy to reproduction, rapidly outnumbering the more industrious cells. (Cancer is an example of cheaters within our own bodies — genetically distinct cells that act in their own best interest, endangering the larger entity.)
In snowflake yeast, the single-cell bottleneck means that cheater cells are stuck with a community of cheaters. The group won’t be able to survive on its own. “The simplest and most general explanation for why multicellular organisms pass through a single-cell stage is to ensure that all the cells composing the organism are as close to perfectly related to each other as they could be,” said Rick Grosberg, an evolutionary biologist at the University of California, Davis. “Everyone shares the same genetic interests.” The bottleneck forces an alliance.
Perhaps the most important argument in favor of snowflake yeast’s status as a multicellular creature is that natural selection is acting on the snowflake as a whole. In a new set of experiments, Ratcliff’s team is pitting snowflake yeast against floc yeast in a head-to-head battle. Preliminary results show that over and over again, snowflakes drive flocs to extinction. “They are evolving in the same way that multicellular organisms are,” Ratcliff said. “Selection acts on groups and the groups respond to selection.”
Yet snowflake yeast fails one key test of multicellularity: indivisibility. “We can’t be chopped into smaller parts and maintain the properties of the whole,” Michod said. Snowflake yeast can. Because of this, “I think snowflake yeast are not really true multicellular organisms,” Michod said. “But they are certainly on their way.”
The snowflake yeast strains have now been evolving for more than a year, and they continue to change, getting bigger and rounder with each generation and sinking faster than their ancestors. “We can see these Darwinian processes playing out in the lab over thousands of generations,” Ratcliff said.
The ongoing transition is giving researchers a powerful tool for studying the genetic foundations of multicellularity. Ratcliff has already identified one of the genetic mutations that make it possible for snowflake yeast cells to stick together in their particular way. He hopes to identify additional mutations involved in the switch to multicellularity, which will illuminate the mechanisms underlying the process. Even though snowflake yeast might not directly reveal how multicellularity first evolved on Earth, it should highlight the general evolutionary processes needed to get there. The fact that basic multicellularity is so easy to create is “a profound insight if not a complete insight,” Grosberg said.
What’s more, lab-evolved multicellularity isn’t limited to yeast. Scientists can drive other single-celled organisms to multicellularity as well. Ratcliff and collaborators Matthew Herron and Frank Rosenzweig, both biologists at the University of Montana in Missoula, showed that they can transform the single-celled alga Chlamydomonas reinhardtii into a multicellular entity. This is particularly important because one of the criticisms of Ratcliff’s yeast work is that some natural yeasts have multicellular forms, meaning that his experiments might simply be restoring a latent talent.
The researchers ran similar experiments to those in yeast, selecting for cells that sink the fastest. But they also employed a selective pressure that algae are more likely to experience in nature: predators, such as paramecia, that can’t eat larger multicellular blobs. The predator-driven strains developed a different sort of multicellularity from the gravity-induced versions. These multicellular Chlamydomonas have spherical blobs of cells contained within the same cell wall.
It’s not so surprising that algae came up with different routes to multicellularity. The transformation evolved independently in plants, animals and fungi dozens of times, maybe more. So there are likely different solutions to the problem of making the transition. “What are the suite of possible genetic keys that unlock the door to multicellularity?” Rosenzweig said. “That’s one thing to be gained by comparing different systems.”
Researchers also want to know how these clusters become more complex, partitioning jobs like a well-run factory. “How does a multicellular organism make that next great leap to differentiated cell types that work cooperatively in the organism?” Rosenzweig said.
Rosenzweig cites an ongoing experiment in his lab with Chlamydomonas. Single-celled algae have flagella, taillike appendages that propel the cell toward light. The multicellular versions of Chlamydomonas also have flagella, but theirs are trapped and useless inside the larger cell wall. “It’s like being in a lifeboat and having your oars stuck in the air, not the water,” Rosenzweig said. To use their flagella, Chlamydomonas will have to evolve ways to get them in the right place and to coordinate their movement.
Ratcliff hopes his snowflake yeast will eventually develop this kind of complexity. Perhaps the mechanism that drives cell suicide will evolve a more sophisticated function. Perhaps, given enough time, the new multicellular forms will evolve even more surprising capabilities, just as the transition to multicellularity billions of years ago ushered in a world of large and complex life. “One of the reasons the research is so interesting is that it describes the beginning of a bona fide major transition in real time,” Kerr said.
By Shelley Littin, iPlant Collaborative
Original Story: http://www.iplantcollaborative.org/blog/news/iplant-hosts-platform-field...
Researchers led by a team at the Georgia Institute of Technology (Georgia Tech) have developed an online platform that enables plant scientists to obtain quantitative phenotype information on the root systems of plants imaged in the field.
The platform, called Digital Imaging of Root Traits (DIRT), is now hosted by the iPlant Collaborative’s computational infrastructure, as described in a recent publication in the journal Plant Methods. Researchers anywhere in the world with an Internet connection can access the program by logging into an iPlant account.
The idea is to expedite and simplify the process of collecting measurements of plant roots in the field, said Alexander Bucksch, a research scientist in Joshua Weitz's group at Georgia Tech, and corresponding author on the paper. “Visual phenotypes of a plant can be computed reproducibly with imaging, including features impractical to measure by hand,” Bucksch explained.
The research team spent three years collecting plant root samples at field stations in the United States and South Africa and manually measuring dozens of traits including root density, angles, surface area, number of roots, and many more. They then configured calculations based upon these standardized measurements, to produce a program capable of giving highly accurate measurements for root traits based upon a photograph of roots.
To use the platform, a scientist need only lay out the roots next to a marker for scale and take a photograph, and the program will provide many dozens of phenotype measurements. “DIRT provides a pipeline to move from a field-based image to quantitative data as part of studies by academics and breeders alike,” said Joshua Weitz, associate professor of biology and director of the Quantitative Biosciences Graduate Program at Georgia Tech.
In response to broad interest in using DIRT in the field, Bucksch and his colleagues approached iPlant to host the platform and make it freely available to researchers anywhere. Through iPlant, a user’s data are secure, so that only the account owner and their collaborators may see the results. This makes DIRT a secure, open-access, time saving tool for botanists everywhere.
“Field-based measurements are vital for quantifying traits,” said Nirav Merchant, co-principal investigator of the iPlant Collaborative at the University of Arizona’s BIO5 Institute, and director of Biocomputing at Arizona Research Laboratories. “Automating these methods is essential to support the high throughput nature of analysis. For scientists in the field, DIRT elegantly facilitates the analysis and management of image-based phenotype data by connecting them with scalable cyberinfrastructure and their global community of collaborators.”
“Manually,” Bucksch said, “you cannot measure many dozens of traits in just five minutes, as you can with DIRT.”
The program currently works for nearly all plant root systems. “There are certain traits that only work on monocots or dicots, and we are currently exploring more about this,” Bucksch said, explaining that slight differences in the algorithms account for variation in the plant species.
Already the platform has a substantial user base, with several scientists regularly using it for their root measurements. “Undergraduate students are using DIRT, a Google group is providing user-to-user support, and at least one citizen scientist is currently using it,” said Bucksch.
"DIRT seems especially useful in my work because a plant is a lot like an iceberg: Most of it is totally hidden beneath the surface," said Tim Zebo, a recently retired electronics engineer turned hydroponics and aeroponics systems researcher. Dr. Zebo is analyzing the roots of plants grown in liquid nutrients because, in this era of rapid climate change and major droughts, those plants require less than 10 percent of the water needed for soil-grown plants. He plans to use DIRT to better understand root system architectures to increase production and reduce time to harvest.
For plant scientists and breeders, Bucksch said, root traits are key. “The root is important to nutrient uptake,” he said, continuing “and understanding how environmental and growth factors influence root traits is vital to developing crops capable of surviving climate change.
Increased food availability and resilience is necessary to accommodate accommodate rapidly increasing global populations. Plant scientists must work together to understand how plant traits – including root structure and function – affect crop survivability and adaptability. Bucksch and co-authors have developed DIRT with this objective in mind and to enhance the science of root systems.
Their work was supported, in part, by grants from Georgia Tech, the National Science Foundation, the Howard G. Buffett Foundation and the Burroughs Wellcome Fund. Bucksch also thanks iPlant co-principal investigator Nirav Merchant and iPlant senior projects coordinator Martha Narro for their assistance integrating DIRT on iPlant infrastructure. Abhiram Das, a graduate student studying under Bucksch and Joshua Weitz at the Georgia Institute of Technology, led the effort to develop DIRT prior to receiving his doctorate in Bioinformatics earlier this year.
Associate Professor Joshua Weitz has published the first comprehensive book on quantitative viral biology. Quantitative Viral Ecology: Dynamics of Viruses and Their Microbial Hosts establishes a theoretical foundation for modeling and predicting the ecological and evolutionary dynamics that result from the interaction between viruses and their microbial hosts. These go well beyond the viruses we most often think of—influenza, HIV, and Ebola—and include the diverse and abundant viruses that infect single-celled microbes found in oceans, lakes, plants, soil, and animal-associated microbiomes.
Weitz's book addresses three major questions: What are viruses of microbes and what do they do to their hosts? How do interactions of a single virus-host pair affect the number and traits of hosts and virus populations? How do virus-host dynamics emerge in natural environments when interactions take place between many viruses and many hosts? Emphasizing how theory and models can provide answers, Weitz offers a cohesive framework for tackling new challenges in the study of viruses and microbes and how they are connected to ecological processes—from the laboratory to the Earth system.
In the water above natural oil seeps in the Gulf of Mexico, where oil and gas bubbles rise almost a mile to break at the surface, scientists from the Georgia Institute of Technology, Columbia University and Florida State University have discovered something unusual: phytoplankton, tiny microbes at the base of the marine food chain, are thriving.
The oil itself does not appear to help the phytoplankton, but the low concentration of oil found above natural seeps isn’t killing them, and turbulence from the rising oil and gas bubbles is bringing up deep-water nutrients that phytoplankton need to grow, according to a study appearing January 25 in the journal Nature Geoscience. The result is phytoplankton concentrations above oil seeps that are as much as twice the size of populations only a few kilometers away.
“This is the beginning of evidence that some microbes in the Gulf may be preconditioned to survive with oil, at least at lower concentrations,” said Ajit Subramaniam, an oceanographer at Columbia University’s Lamont-Doherty Earth Observatory and co-author of the study. “In this case, we clearly see these phytoplankton are not negatively affected at low-concentrations of oil, and there is an accompanying process that helps them thrive. This does not mean that exposure to oil at all concentrations for prolonged lengths of time is good for phytoplankton.”
The research shows that the effects of oil and gas at the sea surface can be very different from the impacts of events such as the Deepwater Horizon spill, said Joseph Montoya, a professor in Georgia Tech’s School of Biology and another of the paper’s co-authors. The research could lead to a reconsideration of the response made to spills.
“There may be different responses by different organisms as we look at different regions of the spill itself,” said Montoya.
The study is the first to demonstrate this kind of teleconnection between the sea floor, subsea floor and microbial processes in the upper ocean, said Andy Juhl, an aquatic ecologist at Lamont and co-author. It also provides insight into how microbes and oil interact under water.
The researchers, along with colleagues in the Ecosystem Impacts of Oil and Gas Inputs to the Gulf (ECOGIG) consortium, began studying interactions around oil seeps after the Deepwater Horizon oil well disaster in 2010 to better understand what happens to the oil during catastrophic gushers and to find ways to better respond to similar disasters in the future. The natural seeps, found in many parts of the Gulf of Mexico, are tiny compared to an oil well blowout. An oil slick from a natural seep lasts between one and seven days and reaches between 1 and 100 square kilometers. In comparison, the surface oil from the Deepwater Horizon well covered about 11,200 square kilometers and persisted for months, Subramaniam said. But natural seeps still produce enough oil and gas that the scientists can smell it at the surface and see the oil bubbles burst.
In the lab, Juhl has been conducting experiments to understand how different concentrations of oil affect different types of phytoplankton. He has found no amount of oil on its own that has a positive effect on phytoplankton. “The direct effect of oil is usually negative, but in some cases small amounts of oil can be outweighed by the positive effect of the nutrients that are tagging along,” Juhl said.
Nigel D’Souza, then a post-doctoral researcher at Lamont, discovered the phytoplankton response to oil seeps while on a ship in the Gulf of Mexico monitoring chlorophyll fluorescence – energy that is emitted as light by compounds inside phytoplankton cells used for photosynthesis. Each time the ship crossed over a known oil seep, he noticed a spike in phytoplankton abundance. It was a Eureka moment, Juhl said. The evidence backed up what Susan Phan, a co-author and Columbia University student working on her senior thesis with Subramaniam, had previously noticed in remote sensing data. The scientists were able to compile multiple lines of evidence through chlorophyll fluorescence, water sampling and satellite images that all supported the idea that phytoplankton were benefitting from something connected with the seeps, even though the seeps were thousands of feet below.
The biggest impact was seen a few hundred feet deep in the water column, at the point where phytoplankton have enough light from above to still grow, and are receiving the most nutrients rising from below. Over oil seeps, D’Souza – who is now at Georgia Tech – found that the population was about double the usual amount. The measurements also showed increases in phytoplankton abundance at the surface.
There are still many questions. For example, scientists don’t yet know which types of phytoplankton are thriving over the seeps, or if some types of phytoplankton in the community are negatively affected by the rising oil. Previous studies have subjected phytoplankton to oil in laboratories to test their sensitivity and found differences in the impact on oceanic versus coastal phytoplankton and differences when phytoplankton were in nutrient-rich or nutrient-poor water, as well as damage to some phytoplankton cells at various concentrations of oil.
The study combined sampling from surface vessels with remote sensing from space.
“Satellite radar data have given us a detailed picture of where natural seeps are concentrated across deep seafloor of the Gulf of Mexico,” said co-author Ian MacDonald, an oceanographer and professor at Florida State University. “Building on this, the present, novel results show biological effects near the ocean surface in areas where seeps are most prolific.”
The research also demonstrates the importance of oceanographic field research in understanding complex ecosystem issues.
“There has been a tendency to rely on autonomous samplers in place of researchers out at sea,” Montoya observed. “For this project, it was really important to have diverse groups of scientists with broad interests working together both at sea and onshore, to tease the system apart.”
The research team plans two pathways of study next: To analyze the behavior of different types of phytoplankton above seeps to better understand how they interact with oil, and to improve understanding of how oil from deep underwater rises to the surface.
The study was part of the ECOGIG Consortium, a multi-institutional group that studies natural oil seeps in the Gulf of Mexico, funded by the Gulf of Mexico Research Initiative. In addition to those already mentioned, coauthors on the study were Mark Hafez, Alexander Chekalyuk, and Beizhan Yan of Lamont-Doherty Earth Observatory; and Sarah Weber of the Georgia Institute of Technology.
This work is supported by The Gulf of Mexico Research Initiative's (GOMRI) ECOGIG consortium, with additional support from National Science Foundation (NSF) grant OCE-0928495. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.
CITATION: N.A, D’Souza, et al., “Elevated surface chlorophyll associated with natural oil seeps in the Gulf of Mexico,” (Nature Geoscience, 2016). http://dx.doi.org/10.1038/ngeo2631
The Torres lab has been awarded a four year, $1.2 million grant by the National Institutes of General Medical Sciences to investigate a newly discovered regulatory mechanism that controls G protein signaling, a process essential for the transduction of extracellular signals (such as hormones, neurotransmitters, and photons of light), and the target of most pharmaceutical drugs.
Spawned by their development and application of a custom bioinformatics software tool (called SAPH-ire) 1, the Torres lab discovered a new way in which G protein signaling is regulated by phosphorylation – an enzyme-driven chemical modification of specific amino acid side chains found in most proteins. The newly discovered phospho-regulatory element, like G proteins themselves, is well conserved throughout eukaryotes, which will enable Torres and his lab to investigate how the element functions across diverse organisms such as budding yeast and humans. The National Institutes of Health grant will also provide funding to determine the biochemical mechanism of G protein phosphorylation – including the enzymes that activate the regulatory element in coordination with other cellular processes including cell division and stress. Through these and other approaches, Torres hopes to determine whether his lab has discovered a protein mechanism that is not only fundamental to the process of G protein signaling in all eukaryotes, but also a possible alternative target for pharmaceutical drug therapies.
Dewhurst, H. M., Choudhury, S. & Torres, M. P. Structural Analysis of PTM Hotspots (SAPH-ire)--A Quantitative Informatics Method Enabling the Discovery of Novel Regulatory Elements in Protein Families. Mol. Cell. Proteomics 14, 2285–97 (2015).
Dr. Frank Stewart in the School of Biology was recently awarded a grant from the Georgia Improving Teacher Quality (ITQ) Grants Program to renew the Summer Workshop in Marine Science (SWiMS). Coral reef collapse, oil spills, and sea level rise are among the most pressing science topics facing policymakers, researchers, and the general public. Understanding these and other issues affecting our oceans is critical to the preservation of marine resources and to a broad education in science. The goal of SWiMS is to use marine science research at Georgia Tech to enhance standards in middle and high school Life and Earth Science education.
Developed by Dr. Stewart in partnership with Gustavia Evans at the Center for Education Integrating Science, Mathematics, and Computing (CEISMC), SWiMS is open to local middle and high school science teachers from high need local education agencies of Fulton County and Clayton County. Through lectures by faculty, discussion and lesson planning sessions, and hands-on lab and field exercises, the 5-day SWiMS course disseminates teaching modules developed around cutting-edge marine science by Georgia researchers. SWiMS modules consist of lesson plans and laboratory exercises that address key marine topics, such as ocean food webs, coral reef decline, and ocean acidification in response to global change. SWiMS 2016 will be held at Georgia Tech from June 27 to July 1. Teachers will leave with enhanced content knowledge as well as lesson plans and schedules for module implementation and evaluation. Each participant will receive 5 professional learning units and a $500.00 stipend. Additional details can be found at https://swimsgatech.wordpress.com/ Details about the ITQ program can be found at https://coe.uga.edu/outreach/programs/teacher-quality
Assistant professor Chong Shin and members of her lab discovered Fhl1b as a novel target of Bone morphogenetic protein (Bmp) signaling. Bmp signaling has been shown to play an essential role in inducing the liver at the expense of pancreas in different animal models. Nevertheless, the identity of downstream gene regulatory networks of Bmp signaling that specify the liver to the detriment of pancreas remains elusive. Moreover, the key question of whether Bmp signaling suppresses pancreas gene program keeping progenitors competent to differentiate into the liver or directly induces the liver gene program has not yet been answered.
Using transcriptome profiling and single-cell level functional analyses in a zebrafish model, Shin and colleagues have discovered Fhl1b as a Bmp2b signaling target that may actively suppress the pancreas gene program to properly modulate liver induction, lineage allocation, and β-cell regeneration.
These findings of Bmp2b regulation of Fhl1bsuggest a new paradigm of how Bmp signaling regulates the cell fate choice of liver versus pancreas and β-cell mass. Furthermore, these results give profound insight into why effective Bmp signaling suppression is critical for the induction β-cells in human pluripotent stem cells (hESCs). Accordingly, a comprehensive understanding of how lineage-specific multipotent progenitors make a developmental choice will shed light on the re/programming of stem/progenitor cells into specific cell lineages, enabling us to generate functionally relevant cells for clinical utility.
This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K01DK081351), the Regenerative Engineering and Medicine Research Center (GTEC 2731336 and GTEC 1411318), the National Science Foundation (1354837), and the School of Biology (Georgia Institute of Technology).
Citation: Xu J, Cui J, Del Campo A, Shin CH (2016) Four and a Half LIM Domains 1b (Fhl1b) Is Essential for Regulating the Liver versus Pancreas Fate Decision and for β-Cell Regeneration. PLoS Genet 12(2): e1005831. doi:10.1371/journal.pgen.1005831
A study from School of Biology Professor Greg Gibson’s group just published in the American Journal of Human Genetics argues that we should be looking not just at the structural parts of genes, but also the regulatory regions around them. The paper demonstrates that there is a burden of rare genetic variants in these regions that associates with abnormal gene expression. It does not show that they cause birth defects, but does suggest that they need to be seriously considered as WGS technology develops.
Gibson explains it in the form of a metaphor about building a house. He says there are two critical components: the bricks and mortar, and the plans for where to put them. If there is a defect in the glass or a crack in a piece of wood, then sooner or later the structure may fall apart. This is what current approaches focus on, the so-called protein coding-regions. But if the architect’s plans call for more windows than the beams can support, or the contractor doesn’t deliver enough concrete, then the consequences can be just as bad.
We now know that a lot more of the genetic component of differences in the way we look and behave, or of what makes us susceptible to different diseases, is in the planning than the structural components. This insight is based on studies of common polymorphisms, namely the millions of genetic differences that we all share. The new study argues that it will also be true of rare genetic variants including new mutations that are specific to a single person.
Graduate student Jing Zhao sequenced the regulatory regions of almost 500 genes from 500 participants in the Georgia Tech-Emory Predictive Health Institute study, and added up the number of rare mutations in people whose expression of those genes was toward the extremes. The result is what she calls a smile plot, because the curve has a high number at either end and low number in the middle. It means that the plans can be off in either direction, making too little or too much transcript for each gene. Explains Gibson, it is as if all the houses with crooked window frames are that way not because of the wood quality, but because each builder made different mistakes when putting the frames in.
Furthermore, there seem to be specific subsets of genes where these events are more or less likely to happen. This is important, because it implies that we may be able to develop algorithms that identify the most likely places for regulation to go wrong, based on the evolutionary conservation of different parts of genes.
Projects such as the President’s Precision Medicine initiative aim to use genomics to help us decipher individual causes of disease. In the next few years, Gibson expects that much larger datasets of tens and eventually hundreds of thousands of people, in many different tissues, will appear. The challenges are as much in the bioinformatics than the technology.
A Burden of Rare Variants Associated with Extremes of Gene Expression in Human Peripheral Blood.
Zhao J, Akinsanmi I, Arafat D, Cradick TJ, Lee CM, Banskota S, Marigorta UM, Bao G, Gibson G.
Am J Hum Genet. 2016 Feb 4;98(2):299-309. doi: 10.1016/j.ajhg.2015.12.023. PMID: 26849112