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Author: Jessica Williamson
Congratulations to our ISG Networking Event poster winners!
MOST CREATIVE:
Foxp1 and Foxp2 regulate cerebellar hemisphere formation by controlling the diversification of Purkinje cells
Presenter name: Nagham Khouri-Farah, PhD Candidate
Affiliated Lab: Li and Cotney Labs, Department of Genetics and Genome Sciences, UConn Health
Abstract: Purkinje cells (PC) are the sole output neurons of the cerebellar cortex and play a pivotal role in cerebellum functioning. Furthermore, PC are presumed to orchestrate cerebellar development by regulating the differentiation of other cerebellar cell types. In the mammalian cerebellum, PC display transient molecular heterogeneity during development. However, the underpinnings of PC heterogeneity remain poorly understood due to the lack of entry to assess individual PC subtypes. Through single-cell RNA sequencing, we identified 11 molecularly distinct PC subtypes in the embryonic mouse cerebellum. Using CyCIF, a highly multiplexed immunofluorescence imaging method, and light-sheet fluorescent microscopy (LSFM), we assigned PC subtypes to their positions and resolved their three-dimensional distribution in the cerebellar cortex. Different subtypes of PCs form distinct cell clusters coinciding with the anteroposterior and mediolateral patterning of the developing cerebellum. Remarkably, PC subtypes display distinctive combinatorial expression patterns of Foxp1 and Foxp2, which have been implicated in developmental speech and language disorders and Autism in humans. Through single-cell genomics and quantitative spatial transcriptomic analysis, we showed that cerebellum-specific deletion of Foxp1 and Foxp2 disrupted a subset of PC subtypes and the formation of the cerebellar hemisphere. Together, our findings demonstrate that Foxp1 and Foxp2 act in concert to govern the differentiation of PC subtypes and, subsequently, control the formation and expansion of the cerebellar hemispheres, which is an innovative feature of the mammalian cerebellum and is involved in higher cognitive functions.
BEST OVERALL:
Novel gene evolution and 3D genome organization
Presenter name: Katherine Fleck, PhD Candidate
Affiliated Lab: Erceg Lab, Department of Molecular and Cell Biology, UConn
Abstract: Genome organization may be intricately tied to regulating genes and associated cell fate decisions. Recent technological advances in mapping of chromosomal interactions and single-cell imaging have provided insights into chromatin organization at various levels including domains, loops, and boundaries. However, how the placements of genes of different evolutionary age in the 3D genome landscape relate to their biological role remains unclear. In this study, we examine the positioning and functional associations of human genes, grouped by their evolutionary age, within the 3D genomeorganization. We reveal that genes of different evolutionary origin have variable positioning relationships with both domains and loop anchors, but remarkably consistent associations with boundaries across cell types. The functional associations of each grouping of genes are primarily cell type-specific, however, those with recently evolved genes are sensitive to 3D genome architecture. Moreover, the sensitivity of such recent genes in diseased state is more pronounced in loop anchors compared to domains. We complement these findings with analysis of the expression from genes of differing evolutionary ages across cell types. Altogether, these distinct relationships between gene evolutionary age, their function, and positioning within 3D genomic features may contribute to understanding tissue-specific gene regulation in development and disease.
ISG Students Featured at the Spring ‘23 Frontiers in Undergraduate Research Symposium
Molecular Biology Projects From the Deep Sea to the Farm
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Brittany Tagg, mentored by graduate student Michelle Neitzey in Rachel O'Neill's lab, is exploring the genome of Tevnia jerichonana, a deep-sea tube worm. T. jerichonana lives in sulfide-rich, low-oxygen hydrothermal vents and has an interesting trick for survival: giving up a typical digestive system for bacterial symbionts that can convert sulfur to energy. Brittany’s project is aimed at figuring out how T. jerichonana has evolved this unique system. She successfully determined a DNA extraction method that yielded good quality DNA for sequencing (a difficult task in marine organisms), with initial bioinformatics assessment indicating enough sequences for genome assembly. Brittany will be attending Cornell’s College of Veterinary Medicine this fall. |
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Emily Trybulec, also mentored by Michelle Neitzey in the O'Neill lab, is studying the genome of deep-sea corals. Corals are susceptible to climate change because they have a harder time keeping up their calcium carbonate structures with higher carbon dioxide input. This challenge is exacerbated by the high-pressure and low-temperature conditions of the deep sea. Emily is sequencing the genomes of deep-sea corals to determine which genes may help them maintain their structures. She has analyzed initial sequencing results, and more sequences will be obtained before genome assembly. Emily is a Junior and is interested in attending graduate school in the future. |
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Emma Forster conducted her research in Dr. Breno Fragomeni’s lab where she investigated the vaginal microbiome of several breeds of cattle. The vaginal microbiome is known to contribute to fertility and healthy delivery in a variety of animals, however, the link between vaginal microbiome and fertility is not clear in cows. Emma amplified the 16S rRNA gene, a genetic tool to identify microbial taxa, in vaginal samples of Angus, Hereford, and crossbreeds of cattle. She found that each breed of cattle had a distinct vaginal microbiome. There was no significant relationship between microbial diversity and pregnancy success, but a larger sample size will be used in the future to investigate the relationship further. Emma is on a pre-vet track and looking forward to starting a manuscript on the initial results of the project. |
From Dirt to Data: Using Genomics to Better Understand Plants
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Harshita Akella, working with graduate student Cynthia Webster in Dr. Jill Wegrzyn’s lab, has been exploring the genome of the ice cream bean tree, Inga vera. I. vera, native to South America, is an important agricultural shade tree and has local medicinal use. There has been very little research into the Inga genus. The inclusion of the first assembled member of the Inga genus will help for a comparative genomics study of I. vera, a few other Inga species, and other common legumes. With an assembled and annotated genome of I. vera, they want to perform a comparative gene family analysis to understand the evolution of the gene families involving nitrogen fixation genes, which are important for legumes. Harshita is interested in attending graduate school in the future with a concentration on bioinformatics. |
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Christopher Guzman and Hannah LeVasseur, also of the Wegrzyn lab, are using genomics to understand the important tree species Juglans cinera, the butternut or white walnut tree. Their project was mentored by graduate students Cynthia Webster and Michelle Neitzey and postdoc Dr. Karl Fetter. They are interested in determining which genes help the tree resist an invasive fungus that is threatening the species. They will compare the butternut/white walnut tree genome to the Japanese walnut tree, Juglans ailantifolia, which is resistant to the fungus. Christopher and Hannah are both interested in attending graduate school. Christopher is interested in studying synthetic biology, and Hannah is planning to pursue a position in a research lab before attending graduate school. |
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Meghan Myles, Madison Gadomski, and Isabella Harding, students in the Wegrzyn lab, are tackling a large problem in molecular biology: most data is unstandardized, producing difficult-to-understand datasets and unequal comparisons between studies. To solve this problem, they are curating the TreeGenes database with the goal of constructing standardized genetic, phenotypic, and environmental information. In the future, Meghan will be applying to post-bac programs in computational biology. Madison would like to do a Master’s in Data Science , and Isabella hopes to attend graduate school after earning her Bachelor’s degree. |
Genes in You & Me: A Focus on Human Health
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Stephanie Schofield, in Dr. Wendy Mok’s lab, has been working with graduate student Travis LaGree on a project investigating bacterial persisters. Bacterial persistence is similar to antibiotic resistance, but instead of being able to grow in the presence of an antibiotic, persisters go into a non-growth state and then switch to growth when the antibiotic is gone. A particular class of antibiotics called fluoroquinolones seems to work well against persisters, especially when combined with glucose. Stephanie conducted experiments to investigate the role of glucose and presented data that indicated that glucose increases DNA replication and transcription, while also influencing the timing of cellular responses that fix DNA damage. Stephanie will be doing research as a Fullbright Scholar in Germany next year and aims to be a genetic counselor in the future. |
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Paul Isaac presented his Diagnostic Genetic Sciences internship research working with Dr. Thi Trinh and Dr. David Peaper at Yale University. Paul is tackling the problem of identifying healthcare-acquired infections (HAIs). HAIs are a particular concern at hospitals where patients are more vulnerable. Paul’s research investigated a bioinformatic approach modeled after a CT Department of Health workflow to identify both bacterial and fungal pathogens, determine sources and potential spread, and identify antimicrobial resistance genes. In cases where the DNA extraction was of good quality, the bioinformatic approach successfully identified pathogens and whether multiple individuals were infected by the same pathogen. The bioinformatics pipeline also recognized antibiotic resistance but was limited to known antibiotic-resistance genes. Future directions are aimed at improving DNA extraction methods for a wide range of pathogens and continuing to test the bioinformatic approach on a larger number of pathogens. Paul will be attending medical school at UConn this fall. |
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Michelle Antony has been investigating cartilage regeneration in Dr. Caroline Dealy’s lab at UConn Health. Humans cannot heal cartilage after a major injury or through loss with aging. Michelle’s project aimed at investigating the role of the Epidermal Growth Factor Receptor (EGFR) in stimulating self-renewing cartilage progenitor cells to participate in repair. Bovine cartilage was used to test the effects of EGFR after inducing scratch injury with and without an inhibitor for EGFR. The results showed that the inhibitor increased lubricin, an indicator of cartilage progenitor cells, highlighting the complexity of the system. Michelle hypothesized that this result may be due to other members of the signaling axis being upregulated to activate the progenitor cell population and compensate for low EGFR signaling after injury. After graduating, Michelle will be doing a post-bac program at the National Institutes of Health and plans to attend a medical degree program in Fall 2024. |
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Kaila Lujambio, working with Dr. Mina Mina and Dr. Sierra Root, presented a study focused on understanding tooth formation and growth. The production of dentin, the tissue that makes up most of our teeth, is formed and maintained by odontoblasts, which have several steps of differentiation. The process is dependent on a transcription factor called RUNX2. The study looked at RUNX2 in mouse incisors, which grow continuously. Immunostaining data indicated that RUNX2 is important to dentin formation, and confirmed that it was present in early-stage, but not late-stage, differentiated odontoblasts. Therefore, RUNX2 expression is early stage-dependent for normal tooth formation. In future studies, incisor development will be analyzed in mice where RUNX2 is not expressed. Kaila plans to attend dental school in the future. |
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Soohyun Oh, working with Dr. Elaine Lee, Dr. Lawrence Silbart, and Dr. Anthony Vella, has conducted a pilot study to investigate the transcriptomic responses of immune cells to acute and acclimated heat stress in humans. Previous studies on a variety of organisms have indicated different signatures of immune-related RNA expression depending on whether the organism was experiencing acute heat stress, was adapted to heat stress, or was heat tolerant. Soohyun’s study then analyzed the differential expression of well-prepared RNA sequencing data and showed that individuals, both men and women, had different quantities and functional genomic landscapes before and after heat acclimation, which may reveal differences in naive versus heat acclimated state. Soohyun is starting the UConn Master's program for Exercise Science in the fall. |
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Bethany Lafontaine presented her research aimed at investigating methods to prevent hyper-inflammatory conditions, particularly associated with Covid-19. In her project, advised by Dr. Lawrence Silbart and Dr. Jessica Malek, she used hamster macrophage cell lines to test the effects of using short interfering RNAs (siRNA) against certain cytokines that can be produced excessively and cause a dysregulated immune response. Bethany showed that several of the cytokines she tested were reduced with the addition of complementary siRNAs. Bethany will be a Medical Laboratory Scientist in the Hematology Lab at Yale New Haven Hospital. |
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Nitanta Garag, mentored by graduate student Katherine Fleck, presented a research project in Dr. Jelena Erceg’s lab related to 3D genome organization and function. Erceg lab students talked about how genome folding and gene regulation may affect genome integrity and cell fates, which can ultimately contribute to a better understanding of chromosome-based human diseases. Nitanta explained that the positioning of genomic regions of varying sequence conservation within the 3D genome architecture. She also discussed the impact of 3D genomic positioning on the functional implications of these genomic regions in health and disease. Nitanta plans to do a post-bac before applying to medical school. |
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Romir Raj, mentored by graduate student Akshada Shankar Ganesh of the Erceg lab, talked about how homolog organization and gene expression relate to each other. He also performed research on chromatin structure and function of homologous chromosomes in Dr. Mayu Inaba’s lab. Together, this work will aid in elucidating homologs, a topic of considerable interest to researchers working on gene expression, genome organization, and development. Romir is currently a biomedical engineering major and is interested in pursuing a career in the medical field as a physician-scientist that performs clinical research. |
The Bewildering B Chromosomes
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Shell Chen and Ayushi Patel, students in Dr. Stacey Hanlon’s lab, study B chromosomes. B chromosomes can affect the organism’s health and have been found in some individuals of many species of plants, insects, and animals, including humans. The students explained that A chromosomes are the typical necessary chromosomes species have while B chromosomes are extra and non-essential. Shell and Ayushi explained that there is evidence that the fruit fly B chromosomes come from chromosome 4. Their project indicated that the presence but not quantity of B chromosomes can affect eggs having an incorrect number of chromosome 4. This Fall, Shell will be starting a Ph.D. program at Brandeis University in Molecular and Cellular Biology, while Ayushi will be working as a medical scribe and applying to medical school. |
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Ryan Gado, also of the Hanlon lab, is studying genetic factors that determine the number of B chromosomes in fruit flies. B chromosomes do not play by the rules of Mendelian genetics and flies can pass numerous copies to the next generation, but little is known about which factors control this process. Ryan presented evidence that some gene(s) on chromosome 3 in addition to a gene called matrimony affect how many B chromosomes get passed on to the next generation of flies. Ryan is a rising Senior with an interest in attending a Ph.D. program in the future. |
The Making Sense of Senses
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Claire Sullivan, a student in Dr. Karen Menuz’s lab, talked about how insects use odor detection to find both food and hosts. For example, mosquitoes can use olfactory receptors to smell small amounts of ammonia on people’s skin when looking for a blood meal. Claire’s research confirmed that Drosophila fruit flies detect ammonia through their antennae, and showed evidence that several odorant receptors are important for ammonia attraction. In the fall, Claire will be a Research Assistant at the Broad Institute. |
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Tijhuan Grant-Christie, also of the Menuz lab, noted that after sensing an odor, it is just as important to stop sensing it through signal termination in order to detect fluctuations of the odor in the environment. Tijhuan, working with graduate student Sydney Ballou, investigated several odor-degrading enzymes to determine where they were expressed on the antenna, finding that some of these enzymes were broadly expressed along the antenna while others were localized to specific sections. In the future, Tijhuan is interested in continuing her education to become a Physician Associate. |
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Jude Icoy, working with former graduate student Pratyajit Mohapatra in the Menuz lab, presented work on sensing taste. Like people, fruit flies use taste sensing to detect food, but males also use this sense to detect pheromones of female flies before initiating courtship. RNAseq was used to determine which genes were expressed more in the legs of males. Jude found several candidate genes that will be investigated further in mating assays to determine if they are associated with pheromone sensing. Jude plans to work at Albert Einstein College of Medicine for two years before applying to Ph.D. programs in Neurobiology. |
A Resourceful Model for Reproduction Research
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Katarina Yacuk, working with graduate student Rebecca Oramas in Dr, Jianjun Sun’s lab, explained that retaining eggs for too long can lead to decreased viability of embryos. According to students in the lab, fruit fly ovaries are not so different from other organisms. Studying the dynamics of fruit fly reproduction can help us understand fertility challenges and questions in a wide range of animals, including humans. Katarina presented data showing that a particular peptide, DILP8, was important for releasing mature eggs in virgin flies. Katarina will be working in health care as medical scribe and will be applying to medical schools this spring. |
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Haley Grayson, mentored by postdoc Dr. Baosheng Zeng in Dr. Jianjun Sun’s lab, presented research focused on programmed cell death in the ovary, a process that is necessary for proper development and function. Results from the study indicated that the transcriptional factor Serpent (Srp) is important for several stages of cell death in the fruit fly ovary. Haley will be starting a job as a medical scribe and will be applying to medical schools this spring. |
Congratulations to The Kenneth and Paula Munson Family Fund for Student Support in Health Science Fellowship Awardees!
After a competitive selection process, we are pleased to announce six excellent recipients for this year’s The Kenneth and Paula Munson Family Fund for Student Support in Health Science Fellowship, in the amount of $1,000. Congratulations to:
Yetunde Akinlaja, Department of Physiology and Neurobiology
Kate Denegre, Department of Molecular and Cell Biology
Nadine Lebek, Department of Molecular and Cell Biology
Rachael Massey, Biomedical Science
Weizi Wu, School of Nursing
Yiming Zhang, Department of Computer Science and Engineering
Congratulations to Sarah Olson, winner of the 2023 RNA Society Outstanding Career Researcher Award
The RNA Society Outstanding Career Researcher Award recognizes the exceptional contributions of career research scientists in advancing the field of RNA. The 2023 award goes to Sara Olson, who has been a key member in the laboratory of Dr. Brenton Graveley at the University of Connecticut for 21 years and has contributed to 38 published papers. During her career, she has spearheaded a number of important discoveries spanning a wide variety of RNA biology, including the alternative splicing mechanism of the Dscam gene, the characterization of recursive splicing and circular RNAs in Drosophila, the processing of CRISPR RNAs from a multi-cistronic precursor, and extensive characterization of the Drosophila and human transcriptomes as part of the modENCODE, ENCODE and ENCORE collaborative projects. In addition to making key scientific contributions in the Graveley lab, Ms. Olson oversees the DNA sequencing and ancillary equipment within the department, and is responsible for training all personnel on the use of the equipment
ISG Member Ming Xu Wins an Inaugural Hevolution/AFAR New Investigator Award in Aging Biology and Geroscience
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Job Opportunity: Molecular Genetics Laboratory in NYC
Click here to view the job description and application.
UConn Launches New Genetic Counseling Professional Science Masters Degree Program
This program, first of its kind at a public university in New England, is housed in the Institute for Systems Genomics.
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The direct website to the Genetic Counseling Program can be found here: https://geneticcounseling.uconn.edu/
The Genome Ambassadors hosted 7th graders from Martin Kellogg Middle School
Congratulations to the ISG Networking Event Poster Winners!
BEST POSTER:
Purkinje Cell Heterogeneity Orchestrates Mammalian Cerebellar Development
Presenter name: Nagham Khouri-Farah, PhD Candidate
Affiliated Lab: Li and Cotney Labs, Department of Genetics and Genome Sciences, UConn Health
MOST CREATIVE POSTER:
Unique Centromeres & Telomeres in Phased Telomere-to-Telomere Assemblies of Male and Female Tammar Wallabies
Presenter Name: Patrick G.S. Grady, PhD Candidate
Affiliated Lab: R. O’Neill Lab, Department of Molecular and Cell Biology, UConn