The department of Molecular and Cell Biology is in fine fettle, having weathered another challenging year while marking notable successes by faculty, staff, and students.

Our undergraduates have had a fine year: the 150 MCB honors students and university scholars have won 39 SURF awards (Summer Undergraduate Research Fellowships).  Eight of our MCB students are among the 17 University Scholars named this year, and one of our students has been named a Goldwater Scholar, one of 417 awarded nationwide.   Similarly, our graduate student programs are strong and have remained robust during the pandemic.  At present we have about 119 graduate students in our various graduate programs at the Ph.D. and MS levels.  One interesting trend is the growing number of MCB Ph.D. students who are simultaneously earning an MBA degree from the School of Business.  In just the past year, two of our doctoral students have completed these two programs.

In terms of research support, we have continued to produce new grant proposals at a rate that belies the stresses of the pandemic, and to date in this academic year, these efforts have attracted awards totaling more than 3 million dollars.  Some of our faculty are also engaged in research that is translational, with several MCB research programs working to transform scientific discoveries into products, therapies and diagnostics.

We have established new undergraduate summer research fellowships and support significant financial aid for our PSM students.  This is possible with the help of some substantial donations from friends of MCB.

This year we have also successfully recruited a new faculty member to the Microbiology AOC, and are engaged in an ongoing search for a new faculty member in the Structural Biology, Biochemistry and Biophysics AOC.

Faculty excellence has also been recognized in a wide variety of ways including two Fulbright Scholar awards (Lynes and Teschke), election to the Connecticut Academy of Arts and Sciences (Teschke), with a Board of Trustees Professorship and election to the Connecticut Academy of Arts and Sciences (R. O’Neill), and selection as the Edward C. Math mentorship award (Knecht).

Administratively, the department is in transition, with the anticipated shift in faculty serving as department head and associate heads of the department.  I am pleased to share that Dr. Carolyn Teschke will serve as head of MCB, and Drs. Victoria Robinson and Danial Gage will serve as associate heads.  MCB is looking to a bright future with these capable stewards.  I’d like to close with an expression of my sincere thanks to the many faculty, staff and students who have made my tenure as head both interesting and rewarding.

GO:MCB has announced the results from this year's GO:MCB election:

President: Michael Griffith
Vice President: Michelle Neitzey
Treasurer: Dan Phillips
Secretary: Heather Jamieson
Outreach Coordinator: Camille Pearce
Diversity Facilitator: Sophia Gosselin
DEIC Grad Representatives: John Briseno, Patrick Grady, Sophia Gosselin

Congratulations to the new officers and representatives!

The Judith A. and David C. Kelly Summer MCB Research Fellowship program will support three rising senior MCB majors in their research activities in an MCB Faculty laboratory during the summer of 2022. These three fellowships, funded jointly by the Kellys and MCB, in the amount of $8,000 each, are intended to support students with demonstrated financial need who are MCB majors in good standing, and who have career goals aligned with the major. 

MCB Department Head, Michael Lynes,  announced the recipients of the 2022 Graduate and Undergraduate Student Summer Fellowships. These distinguished fellowships are made possible by some very generous donors and are offered on a competitive basis to the most highly qualified students. Please join the department in congratulating them on their accomplishments and demonstrated academic promise.

UConn MCB alumni Jason Bennett, '16 was featured in UConn Today - how his degree led him to be present at the birth of game-changing mRNA technology

“People don’t realize there’s a giant world of biofarma out there where you can try different things and find where your passion lies” Jason Bennett

See story in UConn Today

Two of UConn MCB's PSM alumni have been profiled in the National Professional Science Master's Association's annual newsletter. Marsenia Harrison Mathis, PSM, Microbial Systems Analysis 2009 and Maria Del Carmen Rosas, PSM, Applied Genomics, 2020 were profiled in the association's newsletter, The PSM Alumni and Graduation Chronicle, 2021.

What determines our species - our membership in team Homo sapiens? Or our assigned gender at birth? In part, we are classified by our chromosomes – the supramolecular assemblies that organize our genomes. How chromosomes are passed down through generations, and the consequences of defects in chromosome dynamics on health and evolution are amongst the research themes of our new MCB faculty member Professor Stacey Hanlon.

Professor Hanlon’s introduction to research was as an undergraduate at Texas A&M University, where she was using classic genetic techniques to map a mutation that produced abnormal courtship behavior in the fruit fly, Drosophila melanogaster. Switching to a simpler model system for her doctoral studies at the University of California, San Francisco, Professor Hanlon focused on DNA replication control in budding yeast. Loss of replication control can lead to chromosome instability, and her work in Prof. Joachim Li’s lab focused on how re-replication through the centromeric region affected chromosome segregation. Using modern molecular genetic techniques, Professor Hanlon found that chromosomes with a re-replicated centromere often missegregated during cell division, leading to an abnormal number of chromosomes in the daughter cells. These studies spurred on continued interest in chromosome dynamics. For her post-doctoral work, Professor Hanlon looked for a project that would allow her to continue her interest in chromosome biology while letting her carve out her scientific niche. She joined Prof. Scott Hawley’s lab at the Stowers Institute in Kansas City, MO, just as the presence of B chromosomes in Drosophila melanogaster was becoming known.

B chromosomes have nothing to do with bees but are designated as ‘B’ chromosomes because, unlike the essential ‘A’ chromosomes, they are not critical for growth and reproduction and can be lost. B chromosomes have been known for over 100 years in organisms as varied as plants, fish, mice, grasshoppers, and yes, even bees!** Operationally, B chromosomes are also relevant to humans, since about 0.06% of the population carries small abnormal supernumerary chromosomes that can be associated with intellectual disability or infertility but can also have no recognizable effects.

The D. melanogaster B chromosome that Prof. Hanlon studies appears to have arisen from Chromosome 4 through an unknown mechanism. The B chromosome does not appear to carry any protein coding genes, which begs the existential question: what causes the B chromosome to be, or not to be? Prof. Hanlon’s working hypothesis is that the B chromosomes have been maintained in their original stock through an intriguing phenomenon called meiotic drive. The textbook view of meiosis – the specialized cell division that produces eggs in females and sperm in males – is that each pair of chromosomes are randomly segregated, meaning both copies have an equal chance of ending up in the egg or the sperm. This process is in accordance with Mendel’s Law of Segregation, which predicts that ‘everything is fair’ (based on our interview I gathered that ‘everything is fair’ may be Prof. Hanlon’s favorite expression). When meiotic drive is in effect, however, inheritance of elements such as the B chromosome is anything but random. During her postdoctoral work, Professor Hanlon discovered that the B chromosomes are genetic renegades that cheat during meiosis and are inherited at a higher frequency than expected! Since these B chromosomes do not carry protein-coding genes, what’s the harm of having a few around? It turns out these small B chromosomes pack a big punch during meiosis and can disrupt the segregation of the A chromosomes, which poses a significant genomic conflict: the B chromosomes have a mechanism to act selfishly and get passed to progeny at a high frequency, but natural selection is working against the B chromosomes because their presence wreaks havoc during meiosis and lead to a reduction in fertility. Whether ‘tis nobler of the fly to suffer, the slings and arrows of outrageous fortune, or to take arms against a B of troubles?

Professor Hanlon’s lab is profoundly interested in the genetic factors that resolve the genomic conflict between what is best for the host and what is best for the B chromosomes. What keeps the balance between Mendelian inheritance and natural selection versus the meiotic drive of a selfish genetic element? Are protein gradients involved or does the structure of the B chromosome have to do with its selfish behavior during meiosis? How do cells count chromosomes, to ensure the proper number? How do small chromosomes affect the behavior of the others during meiosis? Answers to these questions will shed fundamental light on our understanding of aneuploidy, the occurrence of one or more extra or missing chromosomes. Aneuploidy occurs due to errors in chromosome segregation, and when this occurs during meiosis, it can result in infertility and disorders such as Down syndrome. From an evolutionary perspective, we can expect new insights into how and where new chromosomes arise, as well as what can influence their frequency of formation such as maternal age or exposure to a small molecule. Equally important for the progress of the research, is the recruitment of talented students. In the Hanlon lab, students can expect to receive training in modern molecular biology techniques, classic genetics, and cytogenetics, amongst other areas. Everything being fair, we expect the Hanlon lab to provide many contributions to our understanding of chromosome segregation, meiotic drive, and genomic conflict in the years to come.
** (Comp Cytogenet. 2018; 12(4): 471–482.

Written by Andrei Alexandrescu

Everywhere we look, everything is different. The Universe itself is filled with galaxies and stars that are patchily distributed. Even mathematics is not immune from diversity as some sets of infinities are larger than others. However, most of the familiar diversity, or heterogeneity we encounter every day is biological, from the people we meet to the common trees seen in our neighborhoods. Therefore, diversity seems a universal foundational principle, especially for the biological world and even its human witnesses. Indeed, each individual human has a genome containing two versions for most of the approximately 25,000 genes distributed over our 46 chromosomes (i.e., two haploid genomes, one each from our biological parents). Amazingly, that chromosomal and genetic diversity adds up to approximately six billion nucleotide base pairs, which is about two meters when stretched out end-to-end. That DNA must fit into a cell nucleus 10 millionths of a meter in diameter. This is no trivial feat, and it requires tremendous amounts of DNA folding, a process that generates remarkable physical structure inside each finitely sized nucleus. However, critical answers remain largely a mystery as little is known about how DNA is “packaged” within the nucleus or how that packaging affects gene expression and its regulation, which must take place in the nucleus as well. Luckily, these vastly important answers are being pursued by one of our newest MCB faculty members Dr. Jelena Erceg.

To find those answers, Dr. Erceg first sought a foundational understanding of how regulation of gene expression occurs, which she embarked upon as an undergraduate researcher at the University of Zagreb, Croatia. There, she did research on DNA methylation of pumpkin chromosomes and wrote a thesis on research that characterized enhancer traps into hox gene clusters. Enhancer traps are a genetic construct containing a transposable element and a reporter gene like LacZ that inserts itself randomly into chromosomes and is used as a proxy for detecting the expression of nearby genes. This molecular biology technique allows researchers to map the location of enhancers (often called transcriptional factors) on chromosomes that hopefully leads to understanding wholesale gene expression patterns across the entire genome. Such knowledge is critical for understanding how a fertilized cell becomes a fully developed animal. Hox genes are important for animal embryo development and determine how, when, and which cells change into different kinds of cells with altered functions.

Dr. Erceg’s undergraduate experience and initial understanding of gene expression eventually led her to a graduate program doing research as a Louis-Jeantet Foundation Ph.D. student in the laboratory of Dr. Eileen Furlong at EMBL in Heidelberg, Germany where she further studied the regulation of gene expression during embryonic development. It was during her time in Heidelberg when she discovered that the same enhancer functions in two different developmentally related tissues, where one enhancer will have a flexible motif and the other a conserved motif. Thus, enhancer sequence variation between individuals, including small deletions or insertions can have dramatic tissue specific effects during development. In a related discovery, Dr. Erceg also uncovered that some regulatory elements have dual activities. Her findings indicate tight regulation of transcription occurs during key developmental transitions, where specific patterns of gene transcription may need to be active in one cell but repressed in another. “Dual elements” says Dr. Erceg “may ensure a finely tuned initiation or silencing of transcription during rapid cell fate decisions,” which are critical to embryonic development.

Dr. Erceg’s undergraduate and Ph.D. research thought of chromosomes and their enhancers as two-dimensional linear objects, which of course, they are. However, as an EMBO Long-Term postdoctoral fellow at Harvard Medical School in the laboratory of Dr. C.-ting Wu, Dr. Erceg examined how gene expression regulation occurs within all three dimensions of the space-limited chromosome filled nucleus, which reflects perhaps more accurately the “real world” by considering the effects of extensive DNA folding and the creation of physical structures. For example, can distantly located homologous genes or enhancers on the same or different chromosomes involved in similar roles be much closer in 3-dimensional space within the nucleus? If so, how does that impact the regulation of gene expression? Thinking 3-dimensionally allowed Dr. Erceg to gain valuable insight into these important questions, demonstrating indeed there is extensive chromosomal organization in the nucleus that creates global connections between chromosomes and homologous genes, allowing an all-important road map to be drawn regarding how gene transcription is governed. “This work,” says Dr. Erceg, “provides an exciting framework to accommodate all types of inter-chromosomal interactions”. Her time at Harvard was also spent developing two complementary, innovative, and cutting-edge technologies. The first one allows researchers to distinguish between intra-chromosomal and the understudied inter-chromosomal interactions and contact points. The second one enables super-resolution single-cell imaging of chromosome organization. Both techniques will contribute to a better understanding for how transcription is regulated.

Despite all the recent advances in understanding chromosome organization and the relationship between 3D genome organization and DNA sequence evolution, there remain countless unanswered questions. Dr. Erceg has already cut a substantial path through the thickets of gene expression regulation, and she plans a career here at UConn that will unveil many more answers to the current mysteries, which she believes may possibly lead to personalized medical treatments for many genetic and developmental diseases.

Written by Thane Papke