Alexander "Sasha" Gimelbrant, Ph.D.
Altius Institute for Biomedical Sciences

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Alexander “Sasha” Gimelbrant is an Investigator at Altius Institute for Biomedical Sciences. He has earned his PhD in biochemistry at Moscow State University. After postdoctoral work at the Whitehead Institute and Massachusetts General Hospital, he started his laboratory at the Dana-Farber Cancer Institute. His lab is interested in the epigenetic mechanisms controlling allele-specific expression in development and disease, and the role of these mechanisms in biological variability.

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To help answer Scientific American's question, the authors seek the expertise of Joshua Weitz, Patton Distinguished Professor and Co-Director of the Interdisciplinary Ph.D. in Quantitative Biosciences in the School of Biological Sciences. Two tools built by Weitz's team are included: the Covid-19 Event Risk Assessment Planning Tool that estimates the probabilty of infection in groups of all sizes, given the rates of infection in an area; and a guide for estimating what proportion of each state's population has Covid-19 immunity, either through vaccination or natural infection. 

At the first ever CMDI-CDC Meeting on Infectious Disease Dynamics, held on June 10, 2021, researchers from the Centers for Disease Control and Prevention (CDC) and the Center for Microbial Dynamics and Infection at Georgia Tech (CMDI) came together virtually to discuss ecological and evolutionary perspectives on infectious disease dynamics.

“The mission of the CMDI is to transform the study and the sustainable control of microbial dynamics in contexts of human and environmental health,” notes Sam Brown, director of CMDI and professor in the School of Biological Sciences at Georgia Tech. “In keeping with this work, the CMDI-CDC Meeting on Infectious Disease Dynamics brought together these scientists as neighbors in Atlanta, and as organizations committed to the research of disease prevention and control.”

“In addition to showcasing the overlapping research interests of the CMDI and the CDC, the symposium also offered members of the Georgia Tech and CDC communities an open platform to ask questions of researchers in real time, as well as an opportunity to make new connections and encourage collaboration,” says Jennifer Farrell, a Ph.D. student studying microbiology at Georgia Tech who helped organize the meeting.

Farrell shares:

The online symposium drew 178 participants from across Georgia Tech and the CDC, setting the stage for continued communication and collaboration between the two institutions. The day kicked off with opening remarks from Brown and Juliana Cyril, director of the Office of Technology and Innovation, Office of Science, CDC.  Cyril and Brown each highlighted the unique relationships and collaborative potential between the two organizations.

Talks spanned pathogen systems, from the bacteria Pseudomonas aeruginosa and Streptococcus pneumoniae (Rich Stanton and Davina Campbell, CDC; Pengbo Cao, CMDI; Bernie Beall, CDC), to colonization dynamics of the fungal pathogen, Candida auris (Joe Sexton, CDC), to shield immunity in SARS-CoV-2 (Adriana Lucia-Sans and Andreea Magalie, CMDI).

Talks were further divided into research themes such as biofilm control (Pablo Bravo, CMDI; Rodney Donlan, CDC; Sheyda Azimi, CMDI) and microbiomes in infection (Commander Alison Laufer-Halpin, CDC; Jennifer Farrell, CMDI).

“In line with the commitment of the CMDI to promote trainee career development, the CMDI-CDC Meeting on Infectious Disease Dynamics was organized and run by Center graduate students and post-doctoral scientists, and CMDI talks were presented exclusively by Center trainees,” adds Farrell. “We look forward to continuing the conversation with our CDC colleagues in the future!”

Two charitable foundations have announced their support of research at the Georgia Institute of Technology that could change the basic understanding of DNA, potentially leading to new treatments for degenerative diseases.

The W.M. Keck Foundation and the G. Harold and Leila Y. Mathers Foundation have awarded grants of $1 million and $300,000, respectively, to boost the research of Francesca Storici, professor in the School of Biological Sciences and principal investigator for the projects. Both grants are directed toward decrypting the hidden message of ribonucleotide incorporation in human nuclear DNA.

The Mathers Foundation will cover work with the Storici lab only. The Keck Foundation is supporting a collaborative effort between Storici and Natasha Jonoska, professor of mathematics at the University of South Florida. Both Storici and Jonoska are founding members of the Southeast Center for Mathematics and Biology.

Full article by Jerry Grillo may be found here: https://research.gatech.edu/new-grants-could-transform-scientists-understanding-dna  

 

As the academic year comes to an end, the Student Government Association (SGA) is welcoming its new leadership. Samuel Ellis and Ajanta Choudhury were recently sworn in as the undergraduate SGA president and executive vice president, respectively. And Stephen Eick and PJ Jarquin will be taking over as graduate SGA president and executive vice president.

Eick, a Ph.D. student in computer science, comes from GSGA’s legislative branch, the Graduate Student Senate (GSS). Jarquin, a Ph.D. student in biomedical engineering, has spent his time in GSGA on the executive side, serving as vice president of campus services this year. He and Eick believe that, together, their experiences in different parts of student government will allow them to approach problems in a balanced way.

Ellis and Choudhury met in the Undergraduate House of Representatives (UHR) during the 2019-20 school year. After that, Ellis, an international affairs major, became vice president of external affairs, while Choudhury, a biology major, took a year away from SGA. They hope that being able to see SGA from different perspectives will help them provide solutions and address issues.

As their terms get underway, both teams are ready to jump into advocating for students. For the undergraduate executives, this largely focuses on academic policies, changing how students interact with the Office of Student Integrity, and helping with the shift to in-house dining in the fall. The graduate executives, meanwhile, are starting off by trying to help increase and consolidate mental health resources across campus, as well as advocate for new ways to support graduate researchers. Both groups agree that as Tech transitions toward a more familiar semester in the fall, they want to be involved in making sure that transparent, robust policies are in place to keep students safe.

Both sets of executives also share the desire to strengthen their particular side of SGA, which they feel will allow them to better advocate for students’ needs. For example, Eick has a goal of filling every seat in GSS by the end of the year.

“We hold ourselves back when we don’t have people engaged,” he said. As a member of GSS, Eick was the only representative for the College of Computing, which usually can have as many as nine representatives. He sees this as an excellent opportunity to increase both participation and diversity within GSGA.

“We want to make sure that we’re reaching different parts of campus whose voices aren’t usually heard,” Ellis said. For him, this means bringing new people into USGA by creating a recruitment chair position, as well as connecting people outside of the organization with Institute-wide committees where their input would be useful.

Each new executive also has a policy that they’re particularly excited to work on. For Ellis, it’s finding a way to address the problem of students experiencing homelessness; Choudhury wants to improve infrastructure for students with disabilities. Eick is passionate about building a participant recruiting board for research studies across campus to strengthen graduate student research, while Jarquin plans on advocating for more LGBTQ+-friendly health resources.

The new SGA leadership is ultimately humbled by the opportunity to serve their fellow students.

“To be in this role is to empower and uplift those in the same way that I felt empowered and uplifted by former executives in student government,” said Choudhury. “Being in this role isn’t just about improving the student experience, but really empowering the next generation of student leaders.”

“Coming from an immigrant father, being raised in the South, and being gay, it’s important for me to be in a role as visible as this,” Jarquin said. “It really is an honor to be in the position to fight for all graduate students.”

Applications are currently open to be an executive committee chair for undergraduate SGA; applications are rolling, but those interested should apply by Friday, May 7, to be considered. Learn more about each committee here. Elections for GSS and first-year representatives for UHR will happen in the fall; view the full list of seats in GSS and UHR.

Sam Brown, professor in the School of Biological Sciences, is one of 65 new fellows elected to the American Academy of Microbiology's class of 2021. 

"I’m thrilled to join the American Academy of Microbiology," Brown says. "I want to offer a huge thanks to my lab, past and present, and colleagues around the world who made this recognition possible, and who make science so much fun. Looking forward, I’m excited to continue building microbiology research on campus, through our Center for Microbial Dynamics and Infection (CMDI)."

Information on one of Brown's recent research studies can be found here.

 

Chronic itch is defined as itch persisting for more than six weeks. Because chronic itch is associated with most skin diseases, it is the most common reason for visiting a dermatologist. In addition to being uncomfortable, repeated scratching may result in infection and scarring, making chronic itch socially and occupationally debilitating.

Until recently researchers have experienced difficulty in visualizing the itch-sensing neurons that innervate the skin and are responsible for sensing itch sensation. However, a team of Georgia Tech researchers from the School of Biological Science has combined different cutting-edge techniques to solve this problem.

“We created a new transgenic mouse line that allowed us to, for the first time, see individual itch neurons in the skin,” says Yanyan Xing, a postdoctoral fellow in the Han laboratory. “This is very exciting!” she continued, “Because there are so many neurons in the skin, they often overlap on top of one another. This makes it impossible to determine the size, frequency, or distribution of the neurons.”

Such a state makes it impossible for researchers to perform any sort of detailed analysis on the neurons. For instance, the researchers cannot tell the number of axons per neuron, look for patterns in the spatial density of neurons, or see if the neurons are attached to any specific structures.  “In contrast,” Xing explained, “our transgenic mouse line allows us to perform ‘sparse-labeling’ so that only a few neurons, less than 1%, are visible. Now, we can visualize individual neurons!”

Xing completed this work with a graduate student, Haley Steele, and four other fellow School of Biological Sciences researchers under the direction of Dr. Liang Han. The team published their results, “Visualizing the Itch-Sensing Skin Arbors,” in The Journal of Investigative Dermatology. Specifically, the team looked at a group of itch sensing neurons that are identified by the presence of a single protein, MrgprC11. They, therefore, call this group of neurons MrgprC11+ itch-sensing neurons.

To visualize these MrgprC11+ neurons, the team used a histological staining technique known as PLAP. This technique turns the individual axons of the neurons a dark blue which is visible to the naked eye, even without the use of a microscope.

By visualizing the individual neurons, the team discovered that itch-sensing neurons have large receptive fields. “Receptive fields are the area on the skin that each neuron is responsible for sensing,” Xing explains. “So, if the receptive field is small, such as for touch, you can sense very precisely that something is touching you at this very particular spot. But for the MrgprC11+ itch neurons, we found that they had large receptive fields, three times bigger than for the other neurons we looked at. So that means that when we sense itch, it isn’t confined to a very particular spot. We feel it much more diffusely over a larger area.”

In addition to allowing for the visualization of the itch neurons in the skin, this team’s novel transgenic mouse line also allowed them to learn more about MrgprC11+ neurons in general. For example, they discovered that MrgprC11+ neurons have multiple itch receptors. This is a critical finding according to Xing because “previously nobody was really looking too closely at the MrgprC11+ neurons. Now, that we know that MrgprC11+ neurons are an important itch sensing neuronal population, future researchers may focus significantly more effort on studying MrgprC11+ neurons.”

Genomes are routinely subjected to DNA damage. But most cells have DNA repair systems that enforce genome stability and, ideally, prevent diseases like cancer. The trouble gets serious when these systems break down. When that happens, damage such as unrepaired DNA lesions can lead to tumors, and genomic chaos ensues.

“Double-strand breaks are one of the most dangerous types of DNA damage a cell can experience,” said Chance Meers, a postdoctoral researcher at Columbia University who earned his Ph.D. in molecular genetics in 2019 in the lab of Francesca Storici at the Georgia Institute of Technology. “They inhibit the cell’s ability to replicate its DNA, stalling cell division until the damage is repaired.”

The most accurate pathway of DNA-break repair is by using a homologous DNA sequence to template the re-synthesis of the damaged DNA region. Researchers in the Storici lab previously showed that a homologous RNA sequence could also mediate this break repair, and sought to understand the molecular mechanisms that control this process. They wrote about it in a recently published paper for the journal Molecular Cell.

“This is really about RNA’s capacity to transfer information to DNA that could be used in repairing damage,” explained Storici, professor in the School of Biological Sciences and a researcher in the Petit Institute for Bioengineering and Bioscience at Georgia Tech.

In a 2014 article published in Nature, her team explained how transcript-RNA could serve as a template for the repair of a DNA double-strand break. In this new study, according to lead author Meers, “we found that not only can RNA serve as a template for the repair of double-strand breaks, but that it was modifying genomic information in the absence of double-strand breaks.”

This modification of DNA even in the absence of an induced double-strand break was very surprising to the team. Also unanticipated, said Meers, was that the process of transferring information depended on the presence of an unexpected enzyme, DNA polymerase Zeta. 

“This is quite surprising, because DNA polymerase Zeta is part of a large class of enzymes known as DNA polymerases characterized by their ability to catalyze the synthesis of DNA molecules from a DNA template,” Meers said.

Polymerase Zeta is part of a subset of DNA polymerases known as translesion DNA polymerases, which have unique properties that allow them to synthesize damaged DNA caused by mutagens like UV radiation. Translesion DNA polymerases also are important in cellular processes like the diversification of B-cell receptors used to recognize foreign elements like viruses.

Meers explained that RNA molecules can be thought of as the cache on a computer – or a short-term memory that is not stably maintained. 

“We use a novel assay in which the yeast chromosomal DNA was genetically engineered to contain a piece of DNA sequence that allows it to be removed only in the RNA that is actively transcribed from the chromosomal DNA, generating a change in the RNA sequence but not in the DNA,” he said. 

If this “short-term memory,” in the form of RNA, is transferred back into the DNA sequence during the process of RNA-templated DNA repair, it becomes “long-term memory” stored in the DNA, which can be thought of as the hard drive.  

“We placed this system into a particular gene in yeast, which gives an observable characteristic trait if this process occurred, allowing us to track the repair process,” Meers said. 

Exploiting such an assay, along with the discovery of a new role for DNA polymerase Zeta in RNA-templated DNA repair and modification, the study contains a series of new findings that helped the team better understand the genetic and molecular mechanisms by which RNA can change DNA sequences in cells.  

This research essentially lays the groundwork for exploring the role that RNA can play in modifying genomic sequence and should allow future studies to more directly explore the role of RNA in genomic instability and, in particular, in other organisms, like humans.

This work was supported by the National Cancer Institute (NCI) and the National Institute of General Medical Sciences (NIGMS) of the NIH (grant numbers CA188347, P30CA056036 and GM136717 to A.V.M.), Drexel Coulter Program Award (to A.V.M.), the National Institute of General Medical Sciences (NIGMS) of the NIH (grant number GM115927 to F.S.), the National Science Foundation fund (grant number 1615335 to F.S.), the Howard Hughes Medical Institute Faculty Scholar (grant number 55108574 to F.S.), and grants from the Southeast Center for Mathematics and Biology (NSF, DMS-1764406 and Simons Foundation, 594594 to F.S.). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the NSF.

CITATION: Chance Meers, Havva Keskin, Gabor Banyai, Olga Mazina, Taehwan Yang, Alli L. Gombolay, Kuntal Mukherjee, Efiyenia I. Kaparos, Gary Newnam, Alexander Mazin, and Francesca Storici. “Genetic characterization of three distinct mechanisms supporting RNA-driven DNA repair and 3 modification reveals major role of DNA polymerase Zeta.” (Molecular Cell, 2020) (https://www.cell.com/molecular-cell/fulltext/S1097-2765(20)30554-2

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Writer: Jerry Grillo

Ribonucleotides, units of RNA that can become rooted in DNA during processes such as replication and repair, generally are associated with genomic instability, an increase in mutations, and DNA fragility.

Researchers have been aware of the abundance of ribonucleotides for about a decade, and the lab of Francesca Storici at the Georgia Institute of Technology has been at the forefront, researching the relationship between RNA and DNA in genome stability and instability, and DNA modification. 

“There is much that is unknown about the phenomenon of ribonucleotides in DNA, andit needs to be uncovered,” says Storici, professor in the School of Biological Sciences and a researcher in the Petit Institute of Bioengineering and Bioscience at Georgia Tech, where her lab’s previous studies have led to the development of new-age tools and techniques, to collect and analyze data and answer some of the questions surrounding ribonucleotides.

“It’s important to establish a framework for better directing future studies to uncover physiological roles of ribonucleotides in DNA,” she says. And that’s exactly what she and her colleagues have done in their latest research paper, “Ribonucleotide incorporation in yeast genomic DNA shows preference for cytosine and guanosine preceded by deoxyadenosine,” published recently in the journal Nature Communications.

Namely, they use the tools and techniques they’ve developed over the past few years to characterize sites of ribonucleotide incorporation in DNA, demonstrating clearly that ribonucleotides in yeast DNA are not randomly distributed but show preferences for being incorporated in specific DNA sequence contexts. “We specifically reveal a bias for ribonucleotide incorporation both in yeast mitochondrial and nuclear DNA,” Storici says.

In a previous study published in January 2015, the lab introduced ribose-seq, a high-throughput sequencing technique that allows researchers to establish a full profile of ribonucleotides embedded in genomic DNA, generating large, complex data sets. In late 2018, the lab published its work on a new bioinformatics toolkit called Ribose-Map, which effectively and efficiently transforms the massive amounts of raw sequencing data obtained from the ribose-seq process into summary datasets and publication-ready results.

For their latest work described in Nature Communications, the team deployed ribose-seq to generate the data and Ribose-Map to analyze it, identifying sites of ribonucleotides in yeast DNA and explore their genome-wide distribution. Consequently, the paper’s four co-lead authors included Sathya Balachander (part of the ribose-seq development team and co-author of that paper, now licensing associate for the Bill Harbert Institute for Innovation and Entrepreneurship/University of Alabama-Birmingham) and Alli Gombolay (lead author of the Ribose-Map study).

Contributing equally as co-lead authors of the new research were Taehwan Yang and Penghao Xu, who, like Gombolay, are Ph.D. students in Storici’s lab (where Balachander was a Ph.D. student and postdoctoral researcher).

The team studied three different yeast species and detected a number of similar patterns. In all three species, the deoxyribonucleotide that is immediately upstream of the ribonucleotide was shown to have the greatest impact on the incorporation of ribonucleotides in DNA. “This rule was not clear before,” Storici says. “The study also highlights hotspots of ribonucleotides in DNA sequences containing di- and tri-nucleotide repeats, showing that specific sequence contexts have higher likelihood of ribonucleotide incorporation in DNA. This might be associated with ribonucleotide physiological/pathological functions that are yet to be discovered.”

The lab is now working toward better understanding of how cells control and benefit from ribonucleotide incorporation in DNA by uncovering the patterns and hotspots of incorporation in yeast cells of different genotypes, as well as cells from other species and organisms.

“Now we are interested to see if the rule that we have discovered for yeast applies to other cell types beyond yeast, like human cells for example, and to what extent,” says Storici. “As long term goal, we aim to determine whether there is a sort of language of ribonucleotide incorporation that cells utilize for regulating different cell metabolic functions.”

In addition to those mentioned, other authors of this multi-institutional study were Fredrik Vannberg (former professor in the School of Biological Sciences at Georgia Tech and former Petit Institute researcher), Gary Newnam (manager of the Storici Lab), Anton Bryksin (director of the Petit Institute’s Molecular Evolution Core), Havva Keskin (former Storici grad student, now a researcher with Omega Bio-tek), Kyung Duk Koh (former member of Storici lab, now a researcher at the University of California-San Francisco),  Waleed M. M. El-Sayed (former visiting scholar in the Storici’s lab, now researcher at the National Institute of Oceanography and Fisheries in Egypt), and Sijia Tao, Nicole Bowen, Raymond Schinazi, and Baek Kim from the Emory School of Medicine’s Department of Pediatrics.

  

For Lewis Wheaton, Black History Month is a special opportunity to recognize African-American culture and history. However, Wheaton celebrates diversity and promotes cultural inclusion all twelve months of the year.

“As far back as I can recall, I was taught to value humanity, love those around you, and learn their perspectives,” says Wheaton, an associate professor in the School of Biological Sciences. “Our society is made great not just because of the wonderful blend of culture that we can see all around us, but in our ability to really value our neighbors.”

In both his personal and professional life, Wheaton takes direct action to improve cultural awareness and consider the interests of wider ranges of humanity.

During conversations with colleagues Manu Platt and Anne Pollock, Wheaton realized a lack of interdisciplinary focus on the relationship between scientific study and social influences. Rather than let their ideas end in conversation, the cohort launched Georgia Tech’s working group on Race and Racism in Contemporary Biomedicine in 2015. Today, the group works with various metro Atlanta Colleges to develop programming addressing race and racism in biomedical research.

When Wheaton leaves Georgia Tech’s campus, he continues to promote diversity and inclusion. And, when it comes to encouraging diversity in one's personal life, Wheaton underscores the importance of taking small daily actions to increase one’s cultural awareness.

“Whether in science, public service as an elected official, or in leadership in societies, I do all I can to ensure that we consider the needs and interests of wider-ranges of humanity,” he says.

With the encouragement of his parents and inspiration from Frederick Douglass, Wheaton says he learned the importance of cultural celebration. Each February he devotes extra attention to the black community, sharing many untold and unappreciated aspects of black culture and history. He also takes the time to learn about and celebrate those various wonderful and beautiful elements.

“We can talk to people that aren’t like us, seek opportunities to welcome people from all backgrounds into our organizations, and we can all support (by way of attendance) celebrations of diversity all around campus, even when we do not belong to that diverse group,” says Wheaton.

To read more about Lewis Wheaton:

Lewis Wheaton: Scientist, Citizen, Councilman

Lewis Wheaton: Success Comes with Responsibility

Unlocking the Mind-Body Connection

More Black History Month Features:

Celebrating Black History Month: The Importance of Representation with Crystal Bell

Celebrating Black History Month: Letting Diversity Shine with Alonzo Whyte

Black History Month: "6Ps" Relevant to Academic and Career Success 

By Grace Pietkiewicz, First-Year Student, School of Literature, Media, and Communication

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