Synaptonemal complex threads that connect chromosomes in silkworm oocytes
Fully assembled synaptonemal complexes in fruit fly oocytes
Vilya protein localized to chromosomes during meiotic cell division
An anonymous grant reviewer once wrote that the Hawley lab had “advanced the genetic analysis of meiosis to an art form.” This is still exactly what we are trying to do—by constantly improving the state of the art. For almost four decades, my lab has focused on three major areas of research:
  • how chromosomes can find their homolog during meiosis,
  • the structure and function of the giant protein structure that connects them known as the synaptonemal complex, and
  • how paired homologs can segregate from their partners.



Research

Chromosome synapsis, recombination, & segregation

Our work addresses fundamental questions of meiosis, the process which ensures that gametes receive the correct number of chromosomes. Failures of meiosis are a major cause of aneuploidy, and thus of miscarriage and birth anomalies in humans. We focus primarily on three aspects of meiotic biology: pairing and synapsis; the structure and function of the synaptonemal complex; and a fascinating structure known as the recombination nodule. Although our lab has primarily studied female meiosis in fruit flies (Drosophila) in the past, we are now developing the silkworm (Bombyx mori) as a model organism for meiotic biology.

The process by which homologs pair is, in some ways, one of the fundamental questions of biology: how does a chromosome, identify “self,” from “non-self,” the other chromosomes in the cell. To accomplish pairing, each homolog pair must identify and align with each other and then come into intimate association (referred to as synapsis) along their entire length.  Synapsis is mediated by a meiosis-specific proteinaceous structure known as the synaptonemal complex (SC). Although it was first described a century ago, the mechanism of pairing of homologs remains a mystery.

We are highly focused on understanding the process of pairing, with a focus on understanding the roles of centromeres and heterochromatin in mediating this process.  We are also intent on elucidating the structure and function of the SC and the various roles that it plays in meiosis. Although much is known about the structure and the composition of the SC, critical questions remain regarding its function and the detailed topology of its components.  

Why we care so much about this problem: From a basic research perspective we want to understand meiosis because it is the physical basis of Mendel’s Laws. We also know that a knowledge of meiosis will answer the question of how two thing pair. But, in a broader sense, we are aware that improper meiosis is a common cause of miscarriage, impaired fertility, and birth defects in human beings. We know, for example, that the risk of certain kinds of meiotic failures (the generation of trisomies) greatly increases with advancing maternal age.  The ability to address these issues, and perhaps someday ameliorate them, will come only when we know what goes “wrong” to cause them – and that can come only when we fully understand how meiosis actually works.

Lab members

Scott Hawley, Ph.D.

-Investigator and American Cancer Society Research Professor
-Dean Emeritus, The Graduate School of the Stowers Institute
-Professor of Molecular and Integrative Physiology School of Medicine, University of Kansas Medical Center
-Adjunct Professor, School of Biological Science, University of Missouri at Kansas City

"Teaching is like breathing...
I need to do both to live."

Professional Societies

2001

Fellow, American Association for the Advancement of Science

2006

American Academy of Arts and Sciences

2010

President, Genetics Society of America

2011

National Academy of Sciences

2018-Present

Chair, NIH NICHD Developmental Biology Subcommittee

Honors

1984

Searle Scholar

2008

Excellence in Education Award - Genetics Society of America

2013

George W. Beadle Award Genetics Society of America

2015

American Cancer Society Excellence in Research Award

Education

B.S., Biology

University of California, Riverside

Ph.D., Genetics

University of Washington






Recent Publications

Selected Research Papers
Regulation of Polo Kinase by Matrimony Is Required for Cohesin Maintenance during Drosophila melanogaster Female Meiosis
Curr Biol. 2020.

X chromosome and autosomal recombination are differentially sensitive to disruptions in SC maintenance
Billmyre KK, Cahoon CK, Heenan GM, Wesley ER, Yu Z, Unruh JR, Takeo S, Hawley RS. Proc Natl Acad Sci U S A. 2019;116:21641-21650.

The E3 ubiquitin ligase SINA regulates the assembly and disassembly of the synaptonemal complex in Drosophila females
Hughes SE, Hemenway E, Guo F, Yi K, Yu Z, Hawley RS. PLoS Genet. 2019;15:e1008161. doi: 10.1371/journal.pgen.1008161.

Narya, a RING finger domain-containing protein, is required for both meiotic DNA double-strand break formation and crossover maturation in Drosophila melanogaster
Lake CM, Nielsen RJ, Bonner AM, Eche S, White-Brown S, McKim KS, Hawley RS. PLoS Genet. 2019;15:e1007886. doi: 1007810.1001371/journal.pgen.1007886.

Reviews, Commentaries, Chapters or Books
Alternative Synaptonemal Complex Structures: Too Much of a Good Thing?
[published ahead of print August 13 2020]. Trends Genet. 2020.

Meiosis: Location, Location, Location, How Crossovers Ensure Segregation
Curr Biol. 2020

The Human Genome, A User's Guide.
Third ed: Academic Press; 2011.

Drosophila: A Laboratory Handbook
2nd ed. New York: Cold Spring Harbor Press, 2005. 1409 p.

Advanced Genetic Analysis: Finding Meaning in a Genome.
Boston: Blackwell Publishing, 2003. 256 p.

Drosophila Protocols.
New York: Cold Spring Harbor Press, 2000. 724 p.

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News

Former Undergraduate Research, Nazanin Yeganeh Kazemi, receives the Paul & Daisy Soros Fellowship for New Americans.

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Former Undergraduate Researcher, Emily Wesley, represents UMKC at Undergraduate Research Day at the Capitol (URD@C)

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New postdoc, Spencer Koury, joins the lab from the Phadnis Lab at University of Utah.  

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Meiosis is a complex process that most organisms use to generate germ cells (eggs and sperm) for sexual reproduction. Successful meiosis requires the correct amount of genetic material (i.e., chromosomes) to be packaged in each egg or sperm. A failure inthis process results in aneuploidy (the incorrect number of chromosomes), which can cause genetic disorders such as Down syndrome, Klinefelter syndrome, infertility, or miscarriage. There are many steps during meiosis that ensure that the proper number of chromosomes are inherited. One key step is the establishment and maintenance of a multi-protein complex known as thesynaptonemal complex (SC) between chromosomes. This structure allows chromosomes to be paired together and moved to the correct germ cell. We usethe fruit fly to study multiple aspects of the synaptonemal complex. Currently, not much is known about how SC formation is regulated in flies. Previous work in yeast and mice suggest that SC formation is impacted by the modifications made by cyclin­dependent kinases (CDKs). CD Ks are well-known for their role in the generation of new cells, but they are also known to regulate meiosis. Here we removed three predicted CDK binding sites in an SC protein to observe if SC formation was impacted by the loss of CDK regulation. Interestingly, we found that deleting these sites prohibited the SC from fully forming. This suggests that CDK binding sites are important for building and maintaining the SC. Additional work is needed to see if other aspects of meiosis are affected. These results further our understanding of how the SC is assembled and maintained. Understanding how chromosomes are separated into germ cells is critical to furthering our ability to treat infertility and chromosomal disorders.

Virtual Presentation Link:
https://event.crowdcompass.com/ugrd2021/activity/buTdA76CMP
Spencer Koury has joined the Hawley lab to develop and apply chromosome engineering technology. Based on his work at University of Utah, Spencer received NIH funding to synthesize chromosomal inversions to generate trait mapping populations in non-model Drosophila. With a wide variety of applications, Spencer is using synthetic genome rearrangements to dissect selfish sex chromosomes, female meiotic drive, and the crossover patterning mechanism.
The Paul & Daisy Soros Fellowships for New Americans program honors the contributions of continuing generations of immigrants and refugees to the United States. Each year, we support the graduate education of 30 New Americans— immigrants and the children of immigrants—who are poised to make significant contributions to US society, culture, or their academic field. Every Fellow receives up to $90,000 in financial support and they join a lifelong community of New Americans.

Undergraduate Alumnus, Camila Aponte, earns entrance to KU Med school.

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Katie Billmyre receives a K99 award


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"Identification and Characterization of Breakpoints and Mutations on Drosophila melanogaster Balancer Chromosomes" earns G3 Spotlight.

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Former Bluford Healthcare Leadership Institute Scholar and Current UMKC Trustee’s Scholar, Camila Aponte earns entrance into University of Kansas School of Medicine.  Camila notes that “hearing this news was like a breath of fresh air after a long and stressful application process.  This is one of the first steps towards pursuing my dream job, and although I have worked hard to earn the opportunity to study medicine, I am beyond grateful to those who have supported me along the way.”  She is most grateful to Dr. Hawley for “letting me explore the world of research in your lab” and supporting the pursuit of entrance to medical school.  “I will always value you taking time out… to help me in my journey.

”Everyone in the Hawley Lab congratulates Camilla and wishes her well!
Hawley Lab Postdoctoral Researcher, Katie Billmyre, Ph.D., was awarded a Pathway to Independence (K99/R00) fellowship from the NIH. This five-year award is designed to support researchers as they transition from mentored postdoctoral roles into independent research positions. Billmyre, who received a DeLill Nasser award for Professional Development in Genetics from the Genetics Society of America, studies the molecular and cellular mechanisms behind chromosome-specific behaviors during meiosis.
Identification and Characterization of Breakpoints and Mutations on Drosophila melanogaster Balancer Chromosomes has been chosen for the 2020 Spotlight collection of research and scholarship excellence published in the GSA journals. Papers included in the annual collection are selected by editors from both journals and exemplify the types of reports GENETICS and G3 publish. The collection spans topical interests, emerging and classic model organisms, special article formats, and ongoing series, showcasing noteworthy examples of genetics and genomics investigations published in the past year.

https://academic.oup.com/g3journal/pages/spotlight                  

Undergrad research

Want to be an undergraduate intern in the Hawley lab?

The most common way to get an internship in the Hawley lab is to take the Honors Genetics course (BIO206H) co-taught by Dr. Hawley and Dr. Honigberg at the University of Missouri-Kansas City. This gives Dr. Hawley a chance to get to know you, and it gives you a strong background in genetics. We usually ask students to work in the lab for credit for at least a semester. Additionally, the Graduate School of the Stowers Institute offers a fantastic summer program, Summer Scholars, which we encourage students to apply for if they plan to work over the summer. Unfortunately, we are unable to accept high school students as interns.

Featured Undergrads

Emily Wesley, UMKC Undergraduate

Emily has worked as an Undergraduate Researcher in the Hawley lab since January 2018, under the guidance of Dr. Katie Billmyre, a postdoctoral researcher. Recently, Emily completed a published project investigating how genetic background affected synaptonemal complex (SC)maintenance in Drosophila melanogaster. Surprisingly, the genetic background effect worsened when heterozygous for a c(3)G null allele (the transverse filament component of the SC). Additionally, she is working on characterizing a corolla mutant with three deletions in cyclin dependent kinase binding sites. Working as an intern in Dr. Hawley's lab has been an invaluable experience, allowing Emily to fully appreciate the process of scientific discovery. Being able to conduct independent experiments with terrific guidance and mentorship has fostered her curiosity and love of science. Emily would recommend the experience to others who are eager to become closely involved with the research process. She notes that she has gained an abundance of knowledge and skills that will continue to benefit her in a future career in biomedical science.  Emily asserts that the Hawley lab was the best place to begin her career in science and the experiences she has had will serve as a foundation for achieving future goals.

Press
Pre-Med Biology Student Publishes Article in Scientific Journal

Elizabeth Hemenway

Elizabeth’s time in the Hawley lab prepared her to think critically and independently about science, which was a huge part of the application and interview process for graduate school. After her stint as an undergraduate researcher in the Hawley lab, Elizabeth started graduate school at MIT, where she is currently pursuing her Ph.D. in Biology in the lab of Mary Gehring. Scott and Dr. Stacie Hughes, Elizabeth’s mentor in the Hawley lab,  patiently taught her everything from the basics of biology and wet lab work to how to think about the direction of a project in a “big picture” sense, all of which has been invaluable for her graduate studies. The skills and experiences she gathered in the Hawley lab propelled her to her current studies, and she notes she is incredibly grateful for the opportunity to work in the Hawley lab as an undergraduate.

Danny Miller

While in the Hawley lab, Danny used next generation sequencing to study how crossovers and gene conversions are distributed during meiosis, which revealed that unlike crossovers, gene conversions are insensitive to interference and the centromere effect. Separately, he helped determine the structure of some of the most commonly used balancer chromosomes in Drosophila—balancers are multiply inverted and rearranged chromosomes that are used to maintain deleterious alleles in stock and in complex stock construction. The results of these projects allowed the lab to investigate the mechanism behind the interchromosomal effect, or the shift in crossover distribution that is seen when one or more inversions are present during meiosis. This revealed that double strand breaks fated to become crossovers can instead be repaired as gene conversions when those breaks happen near inversion breakpoints and that gene conversions on those chromosomes that can undergo exchange are instead repaired as crossovers.

Danny Miller currently is a combined pediatrics and medical genetics resident at Seattle Children’s Hospital and the University of Washington. Clinically, he is interested in unsolved genetic disorders and how long-read sequencing might be used to both increase the rate of genetic diagnoses and decrease the amount of time it takes to make a genetic diagnosis

Nicole Nuckolls

Nicole Nuckolls grew up visiting Kansas City and fell in love with the city. Because of this, she chose Rockhurst University for her undergraduate degree. While at Rockhurst, she developed a passion for biology and research. Thankfully, there was a world-class research institute right next door to Rockhurst: the Stowers Institute. She joined the Hawley lab as an undergraduate, in her junior year at Rockhurst University. Nicole worked on characterization and identification of new meiotic mutants. In the Hawley lab, they completed a screen, with heavy mutagenesis, to find flies that had low fertility and/or high levels of chromosome segregation errors. Her mentor, Cori Cahoon, taught her the principles of genetics, using Drosophila as a model system, and helped her to fall in love with laboratory research. She became fascinated with the process of meiosis, a fascination that continued to grow in the lab of Dr. Sarah Zanders. She enjoyed studying meiosis in the light of genetic conflict and completed her Ph.D. program at the Graduate School of the Stowers Institute in August 2020.

Working with Scott Hawley was a dream come true for Nicole. She has noted that she would not be the scientist she is today without the experience in his lab. She still uses genetics as her primary tool of research and is still studying the principles of cell division and meiosis, now as a postdoc. She is currently working as a postdoc at the University of Colorado in Julia Cooper's lab, studying fission yeast telomeres and centromeres.  The training she received in the Hawley lab, not only in scientific method and experimental procedures, such as microscopy and genetics, but generally as a scientist, have lasted her throughout her studies. She notes these skills and preparatory learning will continue to guide her in her future career. Scott taught her to think critically and how to mentor the future generations of scientists (and truly enjoy it), while instilling a love of meiosis, genetics, and science, in general.

Nazanin Yeganeh Kazemi

Nazanin was an undergraduate researcher in the Hawley Lab during her junior and senior at University of Missouri - Kansas City. She earned a B.S. in Biology and Chemistry from UMKC in 2015 and started training at the Mayo Clinic Medical Scientist (MD-PhD) Training Program. Nazanin is currently a sixth-year student in the program. She is completing a Ph.D. in Immunology and will be serving as a Fulbright Scholar, conducting research at the University of Geneva, this year. The skills learned in the Hawley Lab continue to serve in her current research, and Dr. Hawley has been an incredible resource as she explores more opportunities in training.

Scott Beeler

Nazanin was an undergraduate researcher in the Hawley Lab during her junior and senior at University of Missouri - Kansas City. She earned a B.S. in Biology and Chemistry from UMKC in 2015 and started training at the Mayo Clinic Medical Scientist (MD-PhD) Training Program. Nazanin is currently a sixth-year student in the program. She is completing a Ph.D. in Immunology and will be serving as a Fulbright Scholar, conducting research at the University of Geneva, this year. The skills learned in the Hawley Lab continue to serve in her current research, and Dr. Hawley has been an incredible resource as she explores more opportunities in training.

What we're reading

A sampling of recent literature of special interest to the Hawley Lab, with occasional comments from lab members.
Failure to recombine is a common feature of human oogenesis.
Hassold T, Maylor-Hagen H, Wood A, Gruhn J, Hoffmann E, Broman KW, Hunt P. Am J Hum Genet. 2021 Jan 7;108(1):16-24. doi: 10.1016/j.ajhg.2020.11.010. Epub 2020 Dec 10. PMID: 33306948.

Single-Molecule Tracking of Chromatin-Associated Proteins in the C. elegans Gonad.
von Diezmann L, Rog O. J Phys Chem B. 2021 Jun 7. doi: 10.1021/acs.jpcb.1c03040. Online ahead of print. PMID: 34097417.
           

Let's get physical - mechanisms of crossover interference.
von Diezmann L, Rog O. J Cell Sci. 2021 May 15;134(10):jcs255745. doi: 10.1242/jcs.255745. Epub 2021 May 26. PMID: 34037217.
                   
‍Meiotic sister chromatid exchanges are rare in C. elegans.
Almanzar DE, Gordon SG, Rog O. Curr Biol. 2021 Apr 12;31(7):1499-1507.e3. doi: 10.1016/j.cub.2020.11.018. Epub 2021 Mar 18. PMID: 33740426 Free article.

Synaptonemal Complex dimerization regulates chromosome alignment and crossover patterning in meiosis.

Gordon SG, Kursel LE, Xu K, Rog O. PLoS Genet. 2021 Mar 17;17(3):e1009205. doi: 10.1371/journal.pgen.1009205. eCollection 2021 Mar. PMID: 33730019 Free PMC article.

Meiotic DNA break repair can utilize homolog-independent chromatid templates in C. elegans.

‍Toraason E, Horacek A, Clark C, Glover ML, Adler VL, Premkumar T, Salagean A, Cole F, Libuda DE. Curr Biol. 2021 Apr 12;31(7):1508-1514.e5. doi: 10.1016/j.cub.2021.03.008. Epub 2021 Mar 18. PMID: 33740427 Free article.

Elevated Temperatures Cause Transposon-Associated DNA Damage in C. elegans Spermatocytes .
Kurhanewicz NA, Dinwiddie D, Bush ZD, Libuda DE. Curr Biol. 2020 Dec 21;30(24):5007-5017.e4. doi: 10.1016/j.cub.2020.09.050. Epub 2020 Oct 15. PMID: 33065011 Free article.





Join us!

Interested in becoming a member of the Hawley Lab?


For motivated undergraduates, please refer to the Undergraduate Research tab for information on how to become an intern in the lab.

Students with an interest in conducting their PhD thesis work in the Hawley Lab should apply through the Graduate School of the Stowers Institute for Medical Research. Doctoral students from other PhD programs should contact Dr. Hawley directly at rsh@stowers.org

Dr. Hawley is accepting applications for independent, ambitious postdoctoral scholars on a rolling basis. To apply, please send a current CV, a brief description of your doctoral research, and a paragraph summarizing what you are most interested in working upon joining the lab.

Hawley Lab


Stowers Institute for Medical Research
1000 E 50th Street
Kansas City, Missouri 64110

KVirden@stowers.org
(816) 926-4000