Danae Schulz, Ph.D.
Department of Biology
Harvey Mudd College
Trypanosoma brucei, the causative agent of African sleeping sickness, is transmitted to its mammalian host by the tsetse. In the fly, the parasite’s surface is covered with invariant procyclin, while in the mammal it resides extracellularly in its bloodstream form (BF) and is densely covered with highly immunogenic Variant Surface Glycoprotein (VSG). In the BF, the parasite varies this surface VSG, using a repertoire of ~2500 distinct VSG genes. Recent reports in mammalian systems point to a role for histone acetyl-lysine recognizing bromodomain proteins in the maintenance of stem cell fate, leading us to hypothesize that bromodomain proteins may maintain the BF cell fate in trypanosomes. Using small-molecule inhibitors and genetic mutants for individual bromodomain proteins, we performed RNA-seq experiments that revealed changes in the transcriptome similar to those seen in cells differentiating from the BF to the insect stage. This was recapitulated at the protein level by the appearance of insect-stage proteins on the cell surface. Furthermore, bromodomain inhibition disrupts two major bloodstream-specific immune evasion mechanisms. Thus, our studies reveal a role for trypanosome bromodomain proteins in maintaining lifecycle stage identity and immune evasion. Importantly, bromodomain inhibition leads to a decrease in virulence in a mouse model of infection, establishing these proteins as therapeutic drug targets for trypanosomiasis. Our 1.25Å resolution crystal structure of a trypanosome bromodomain in complex with a known acetyl-lysine mimetic reveals a novel binding mode of the inhibitor, which serves as a promising starting point for rational drug design. Current efforts in the lab are aimed at optimizing the Cut and Run technique to further characterize bromodomain localization during the transition from bloodstream to insect stage cells. We have also set up reporter systems to be able to carry out high-throughput screens for small molecule inhibitors that initiate a transition from bloodstream stages to the insect stages, and recently used them to screen a library of FDA approved drugs.
Host: Joshua Weitz, Ph.D.
Where is the best place to find living life beyond Earth? It may be that the small, ice-covered moons of Jupiter and Saturn harbor some of the most habitable real estate in our solar system. Life loves liquid water, and these moons have lots of it!
These oceans worlds of the outer solar system have likely persisted for much of the history of the solar system. As a result they are highly compelling targets in our search for life beyond Earth.
Kevin Hand will explain why we think we know these oceans exist and what we know about the conditions on these worlds. He will focus on Jupiter’s moon Europa, which is a top priority for future NASA missions. The talk will also show how the exploration of Earth’s ocean is helping to inform our understanding of the potential habitability of worlds like Europa.
About the Speaker
Kevin Peter Hand is a planetary scientist at NASA’s Jet Propulsion Laboratory (JPL) in Pasadena, California. His research focuses on the origin, evolution, and distribution of life in the solar system, with emphasis on Jupiter’s moon, Europa. His work involves both theoretical and laboratory research on the physics and chemistry of icy moons in the outer solar system.
Hand is the director of the Ocean Worlds Lab at JPL. He served as co-chair for NASA’s Europa Lander Science Definition team. He is the Project Scientist for the Pre-Phase-A Europa Lander mission.
From 2011 to 2016, Hand served as deputy chief scientist for Solar System Exploration at JPL. He served as a member of the National Academies Committee on Astrobiology and Planetary Sciences.
His work has brought him to the Dry Valleys of Antarctica, the sea ice near the North Pole, the depths of the Earth’s oceans, and to the glaciers of Kilimanjaro.
He was a scientist onboard James Cameron’s 2012 dive to the bottom of the Mariana Trench, and he was part of a 2003 IMAX expedition to hydrothermal vents in the Atlantic and Pacific Oceans. Hand has made nine dives to the bottom of the ocean. In 2011 he was selected as a National Geographic Explorer.
Hand earned his Ph.D. from Stanford University and B.S. degrees from Dartmouth College. He was born and raised in Manchester, Vermont.
About the 2019 ExplOrigins Colloquium
This interdisciplinary colloquium and networking event has two goals: (1) to forge connections across Georgia Tech straddling the boundaries between technology development and hypothesis testing in the search for life’s beginnings and (2) to explore collaborative ideas among participants.
- Peter Colin, postdoctoral fellow, School of Biological Sciences
- Zijian Li, Ph.D. student, School of Earth and Atmospheric Sciences
- Tyler Roche, Ph.D. student, School of Chemistry and Biochemistry
- Micah Schaible, postdoctoral fellow, School of Chemistry and Biochemistry
- Pengxiao Xu, Ph.D. student, School of Earth and Atmospheric Sciences
- George Zaharescu, postdoctoral fellow, School of Earth and Atmospheric Sciences
Faculty Advisor: Martha Grover, professor, School of Chemical and Biomolecular Engineering
More information is available here.
A Frontiers in Science Lecture to celebrate 2019, the International Year of the Periodic Table
Why do atoms behave the way they do? Why do electrons form “shells,” as seen in the periodic table?
Why does the first shell hold 2 electrons, the second 8, and the third 18: twice the square numbers 1, 4, and 9?
It took many years to solve these mysteries, and a lot of detective work in chemistry, physics, and ultimately – once the relevant laws of physics were known – mathematics.
Other mysteries remain unsolved, like the mass of the heaviest possible element. This talk will give a quick tour of these puzzles and some of the answers.
About the Speaker
John Baez is a professor of mathematics at the University of California, Riverside, who also works at the Centre for Quantum Technologies, in Singapore. His Internet column “This Week’s Finds” dates back to 1993 and is sometimes called the world’s first blog.
Baez used to work on quantum gravity and pure mathematics. In 2010, concerned about climate change and the future of the planet, he switched to working on a general theory of networks that appear in human-engineered and biological systems.
About Frontiers in Science Lectures
Lectures in this series are intended to inform, engage, and inspire students, faculty, staff, and the public on developments, breakthroughs, and topics of general interest in the sciences and mathematics. Lecturers tailor their talks for nonexpert audiences.
About the Periodic Table Frontiers in Science Lecture Series
Throughout 2019, the College of Sciences will bring prominent researchers from Georgia Tech and beyond to expound on little-discussed aspects of chemical elements:
- Feb. 6, James Sowell, How the Universe Made the Elements in the Periodic Table
- March 5, Michael Filler, Celebrating Silicon: Its Success, Hidden History, and Next Act
- April 2, John Baez, University of California, Riverside, Mathematical Mysteries of the Periodic Table
- April 18, Sam Kean, Author, The Periodic Table: A Treasure Trove of Passion, Adventure, Betrayal, and Obsession
- Sept. 12, Monica Halka, The Elusive End of the Periodic Table: Why Chase It
- October 31, Taka Ito, Turning Sour, Bloated, and Out of Breath: Ocean Chemistry under Global Warming
- Nov. 12, Margaret Kosal, The Geopolitics of Rare and Not-So-Rare Elements
Closest public parking for the April 2 lecture is Visitors Area 4, Ferst Street and Atlantic Drive, http://pts.gatech.edu/visitors#l3
Refreshments are served, and periodic table t-shirts are given away, after every lecture
Promising research toward what could become the first simple and accurate test for the early detection of ovarian cancer could be validated – and expanded – thanks to a significant grant from the Prevent Cancer Foundation.
If validated, the general technique for the work could also have a variety of other applications. “In my dream world, a single blood test could be used to screen for multiple diseases,” said John McDonald, the leader of the research and a professor in the School of Biological Sciences at the Georgia Institute of Technology.
Ovarian cancer is especially dangerous because women often don’t show symptoms until the disease is in an advanced stage and difficult to treat. In contrast, when caught early “about 94 percent of patients live longer than five years after diagnosis,” according to the American Cancer Society.
The problem is that there is no good test for detecting the disease at an early stage.
About seven years ago McDonald and colleagues decided to see if they could change that by merging the disparate disciplines of biology, analytical chemistry and computer science. “Bringing the computer into it was novel at the time,” said McDonald, who is also director of Georgia Tech’s Integrated Cancer Research Center.
His Georgia Tech collaborators on the initial work were Professor Facundo Fernández, the Vasser Woolley Foundation Chair in Bioanalytical Chemistry, and Alex Gray, an assistant professor of computer science (Gray has since left Georgia Tech to become VP for Artificial Intelligence Science at IBM). They were joined by clinical consultant Dr. Benedict Benigno, a gynecological oncologist and CEO of the Ovarian Cancer Institute in Atlanta.
The researchers initially analyzed blood samples from 49 healthy women and 46 with early-stage ovarian cancer. They specifically focused on metabolites in those samples. Metabolites are molecules like fatty acids that our cells produce through enzymatic reactions.
In the molecular equivalent of finding needles in a haystack, they proceeded to analyze some 40,000 metabolites to see if there were any associated with the cancer patients that differed from those in samples from the healthy women. These could be biomarkers for the disease; molecules to screen for in an annual test.
Through a variety of techniques, the team first pared down the original thousands of metabolites to a collection of 255 candidate biomarkers. They then applied machine learning to that set, asking the computer to find any metabolites that were over- or under-expressed in the cancer samples.
“That’s what machine learning is all about,” McDonald said. “The computer is simply looking for correlations in very large data sets, then it comes back to you with what it has found.”
In 2015 the team reported in the journal Scientific Reports the discovery of 16 metabolites that could distinguish women with ovarian cancer from those without the disease with 100 percent accuracy. “Basically we modeled the face of cancer at the metabolic level,” McDonald said.
With the new $100,000 grant, the researchers hope to validate their earlier work with samples from some 1,000 women, as compared to the roughly 100 they originally studied. The new study will also include samples from a much more diverse set of women (the original samples were from Caucasian women).
They also aim to expand the work to look for biomarkers associated with different types of ovarian cancer. “We want to be able to distinguish between a Type II cancer with high malignant potential – one that’s highly likely to spread outside the ovary – and a Type I with low malignant potential. A cancer with high malignant potential you’d want to treat right away, while a cancer with low malignant potential might not require immediate surgery,” McDonald said.
In conclusion, McDonald said, “it’s exciting because the initial results look like [our approach] might work.”
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The annual Clough Art Crawl, a juried, multi-media exhibition of student art inspired by the connection between artistic expression and the world of science, opens Thursday, March 14 and features the exhibition of visual art, literary pieces, and performance pieces.
More than 150 works by Georgia Tech graduate and undergraduate students will be on display at Clough Commons starting at 4 pm, and then the evening continues at 6 pm at the Ferst Center for the Arts with performances by student groups including GT Salsa Club, Taal Tadka, Infinite Harmony and more, with a light reception.
As an added bonus, the opening night at the Ferst Center will feature demonstrations by four innovative Georgia Tech student project teams as they prepare to take part in the 2019 ACCelerate: ACC Smithsonian Creativity and Innovation Festival in Washington, DC this April.
The visual, digital, structural, and literary art works will be exhibited through July at Clough Commons and feature works of art that are inspired by the connection between artistic expression and the world of science. In addition to the artwork created independently by students, included in this year’s Art Crawl are artworks developed as part of three programmatic initiatives at Tech:
- International Year of the Periodic Table: In conjunction with the Georgia Tech College of Sciences and the year-long celebration of the International Year of the Periodic Table of the Chemical Elements, a special section of the CAC will be devoted to art inspired by the periodic table or a chemical element.
- S.A.W.: Science.Art.Wonder is a Georgia Tech student organization that develops art projects based on research currently conducted at Tech and at Emory University. S.A.W. recruits artists (Tech students, faculty, or staff) to create art based on a paired research lab's work.
- Creative Curricular Initiatives: Creative Curricular Initiatives is a program of the Georgia Tech Office of the Arts dedicated to the idea that nurturing students' artistic sensibilities and exposing students to artistic process is essential to developing creativity and innovation. The Art Crawl will include works from three projects that received CCI funding: 1) “Interpretations of Sustainable Business” is a collaborative art project under the direction of Dr. Jennifer Lux, writer and editor for the Ray C. Anderson Center for Sustainable Business. Created by 23 Georgia Tech faculty, staff, students, and alumni., each piece in the 4’ x 5’ artwork relates to environmental sustainability or social dimensions of sustainability; 2) “Like Picasso and Einstein: lines, forms and dimensions” is a gallery exhibition that takes you to the intersection of art and science through student artwork from the Georgia Tech course CEE 8813. A graduate class developed by Dr. Francesco Fedele, this course introduced students to the geometry of space and manifolds, and how these concepts influenced modern arts and sciences; 3) “Shape Machine” is an exhibition of modular printed mylar pieces created by the students of Shape Grammars, the ARCH 4508 class developed by Dr. Athanassios Economou. Students explored fundamentals of spatial and visual composition through a new interactive software, Shape Machine, developed at the Shape Computation Lab at the School of Architecture.
After review by a jury of faculty and staff, winners will receive prizes in each of the categories of visual, digital, structural, literary and performance art; the College of Sciences will also present awards for the top submissions in the special section on the periodic table. Those who view the exhibit at Clough can also vote on a People’s Choice Award. Winners will be announced on March 25.
The annual Art Crawl now runs in the Spring and Fall semesters. Each Art Crawl will have a new theme to inspire student artists and to shape the exhibition. The next Art Crawl will be open for submissions in early fall 2019.
The Clough Art Crawl is coordinated by the Georgia Tech Office of the Arts in partnership with the Georgia Tech Library. For more information please contact firstname.lastname@example.org.
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To celebrate 2019 as the International Year of the Periodic Table, the College of Sciences and the Georgia Tech Office of the Arts have partnered to infuse the 2019 Clough Art Crawl with the spirit of the periodic table.
The annual Art Crawl serves as a unique opportunity for Georgia Tech students to showcase their artistic talents. The theme for the Spring 2019 exhibition is Art Meets Science. In conjunction with Georgia Tech's year-long celebration of the International Year of the Periodic Table of the Chemical Elements, a special section of the Spring exhibition will be devoted to art inspired by the periodic table or a chemical element.
The Art Crawl features art from all students in the following categories:
Visual Art – drawings, paintings, and photography
Digital Art – code-based art, animation, film, and graphic design
Structural Art – sculpture, architecture, crafts, and textiles
Literary Works – poetry/prose, comics, and short stories
Performance Art – dance, live instrumentation, vocal performance, music production, and theater
The exhibit will open on March 14, 2019, at 4 PM. The Art Crawl will award prizes to winners in each category. In addition, College of Sciences will present awards for the top submissions in the special section on the periodic table. Winners will be announced on March 25, 2019.
The visual, digital, structural, and literary art works wil be exhibited through July 31, 2019 at Clough Commons.
The evolution of complex life is an inherently multidisciplinary problem encompassing a wide range of topics, including:
- How do new levels of the biological hierarchy evolve?
- How do interactions between individual organisms contribute to complex phenotypes and behaviors?
- How do social behaviors evolve?
- How do evolutionary novelties emerge and evolve?
- How do organisms drive geochemical cycles and how do geochemical changes influence evolution?
This conference brings together scientists from different backgrounds to discuss these and other important topics about one of the most salient aspects of life: the evolution of complexity.
Register at http://eclife.biosci.gatech.edu/registration/
Below are the topics and confirmed speakers for the conference sessions.The detailed program will be available by April 15, 2019. Please check back at http://eclife.biosci.gatech.edu/program/ for updates.
The evolution of biological complexity
Mechanisms driving evolutionary innovations
Social evolution across scales
Dynamics and evolution of Earth-systems
Principles of social evolution
Origins and nature of life
Information dynamics in evolution
Organizing and Scientific Committees
- Peter Conlin (School of Biological Sciences)
- Zijian Li (School of Earth and Atmospheric Sciences)
- Jennifer Pentz (School of Biological Sciences)
- Pedro Márquez-Zacarías (School of Biological Sciences)
- Gabi Steinbach (School of Physics)
- William Ratcliff (School of Biological Sciences),
- Chris Reinhard (School of Earth and Atmospheric Sciences)
- Peter Yunker (School of Physics)
More information at http://eclife.biosci.gatech.edu/
Ann Chen, Ph.D.
Department of Biostatistics and Bioinformatics
Moffitt Cancer Center
Single-cell technologies allow characterization of genomics, transcriptomes, and epigenomes for individual cells under different conditions and provide unprecedented resolution for researchers. We will first introduce an interactive toolbox SinCHet, which we develop to analyze single cell data for studying heterogeneity using Shannon Profile of at different resolutions. A novel D statistic using area under the Profile of Shannon Differences is devised to detect heterogeneity differences between conditions. Recently, we generalize this tool by implementing de-batching and subpopulation-comparison modules in SinCHet-MS for analyzing single cell mass spectrometry (SCMS) metabolomics data. These suites of tools provide insights into emerging or disappearing subpopulations between conditions, and enable the prioritization of biomarkers for follow-up experiments based on heterogeneity or marker differences between and/or within sub-populations. Two datasets will be discussed during the first part of the talk. The first dataset is a single cell mRNA (scRNA) dataset from two melanoma cell lines and mouse models. The analyses show that melanomas consisted of multiple transcriptional states that they have different drug sensitivities and growth dynamics under drug. The heterogeneity analyses further showed that tumor size in the melanoma mouse model is negatively associated with transcriptional diversity. The second dataset is a SCMS dataset from two colon cell lines. Although unbiased profiling is powerful, we showed that initial experimental design with careful de-batching first is still essential to gain biological insights from single cell data.
About the Speaker
Dr. Chen’s research has been focused on developing statistical methods and computational tools to incorporate multiple omics sources, select biologically relevant markers, and predict clinical outcomes in a unified framework. Her work on Bayesian methodological development of data integration for regulatory network inference and pathway and gene selection for cancer survival prediction facilitates the identification of deregulated pathways with therapeutic relevance in subsets of human cancer. Dr. Chen’s work on nonparametric method improvement for the detection of nonlinear correlation has enabled the identification of key genes for the development of pathological conditions, which might have been missed by traditional methods to detect merely linear relationships. Dr. Chen’s recent work is focused on developing methods to use next gen- sequencing and other omics data to identify novel targetable pathways for melanoma patients, especially for those who did not have commonly known driver mutations.
The evolution of multicellular life from single-celled ancestors is one of the most radical shifts in the history of life on earth, and sets the stage for evolution of more complex life forms. Despite the significance of this transition, we know little about the process by which cells first assemble groups and form multicellular organisms. We study this problem experimentally; a single mutation in the ACE2 gene of Baker’s yeast S. cerevisiae prevents mother and daughter cells from separating after cellular division. These yeast clusters, called ‘snowflake’ yeast, comprise a few hundred cells and grow to a maximum diameter of 200 microns. To evolve larger multicellular size, snowflake yeast clusters must mitigate forces strong enough to fracture cell-cell bonds. After a year of artificial selection for larger multicellular size, five populations of snowflake yeast surprisingly evolved to grow to a maximum diameter of 1 mm. In this work we investigate how nascent multicellular clusters evolve to overcome substantial mechanical constraints and dramatically increase their size.