Tiny parasitic Jewel Wasps and their rapidly changing venom are the subjects of a new study by researchers in the Werren Lab. (University photo / J. Adam Fenster)
Wasp venom holds clues on how genes get new jobs
Amid the incredible diversity of living things on our planet, there is a common theme. Organisms need to acquire new genes, or change the functions of existing genes, in order to adapt and survive.
How does that happen?
A common view is that genes duplicate, with one of the copies picking up a new function while the other copy continues to function as before.
However, by studying tiny parasitic Jewel Wasps and their rapidly changing venom repertoires, the Werren Lab has uncovered a different process that may be widespread in other species as well.
The process involves co-opting single copy genes to take on new functions. In some cases, these genes appear to continue their previous function as well, in other parts of the wasp’s anatomy besides the venom gland. The findings are published in Current Biology.
“It is almost as if they are now moonlighting,” says John (Jack) Werren, the Nathaniel & Helen Wisch Professor of Biology. “They’ve got a day job, and then take on a night job as well. Over time, if the night job works out, they may give up the day job and evolve as a venom specialist. However, in other cases we have found that they stop moonlighting as venom genes but appear to retain their day job.”
“Co-option of single copy genes can be a more rapid mechanism for adapting to a new environment because it does not require the gene to be duplicated first,” notes Ellen Martinson, a co-lead author and postdoctoral research associate in the Werren Lab. “In essence, these wasps are recycling their genes for new functions” says co-lead Mrinalini, a former postdoc in the Werren Lab who has since joined the National University of Singapore, where she studies snake venoms.
The group—which also includes Rochester researchers Yogeshwar Kelkar and Ching-Ho Chang—studied four closely related species of Jewel Wasps. The wasps lay their eggs on the pupae of other insects, after first injecting the pupae with venoms that manipulate the metabolism of the host in ways that make the environment more conducive to their developing young.
Using transcriptome and proteome sequencing, the researchers found that more than half of the venom components in the parasitic wasps resulted from single copy genes that had been co-opted without being duplicated. The composition of the venoms can change quickly, allowing the wasps to adapt to different hosts. For example, even closely related species can differ by up to 40 percent of their venom repertoire.
The group proposes that co-option of single copy genes for new function is not just restricted to parasitoid venoms. Co-option may be common in nature, particularly when organisms are evolving rapidly to changing environments.
With regard to parasitoid venoms, there may be an added benefit, says Werren. The number of parasitoid species is estimated to be as high as 600,000. “The great diversity of parasitoid venoms and abundance of these species, combined with the fact that parasitoid venoms have evolved to manipulate metabolic processes, suggests that they are potentially an immense untapped cornucopia for drug discovery,” Werren says.
John (Jack) H. Werren, the Nathaniel & Helen Wisch Professor of Biology and postdoctoral fellow Ellen Martinson in their lab. (Photo by J. Adam Fenster / University of Rochester)
Children with Fetal Alcohol Spectrum Disorders lag in emotional understanding
A new study reveals that children with Fetal Alcohol Spectrum Disorders (FASD) show a striking developmental delay in their understanding of emotions. Even in those children with an average IQ, researchers found that their emotional understanding lagged two to five years behind their typically developing peers.
“Many children with FASD have considerable difficulty with managing and regulating their emotions and behavior, so it makes sense that they would have delays in emotional understanding,” says Christie Petrenko, assistant professor at Mt. Hope Family Center and lead coordinator of the study.
Researchers from the University of Washington co-authored the study, which was funded by the Centers for Disease Control and Prevention and the National Institute on Alcohol Abuse and Alcoholism.
“People with weaker EU (emotional understanding) may have poor awareness of how their emotions and behavior affect others, which can cause a lot of social problems,” Petrenko explains. “Also, kids with FASD often experience more negative emotions than other kids their age. They may also feel bad about themselves, especially if they don’t get supportive responses from adults in how to cope with strong emotions.”
The researchers conclude that treatments for FASD should focus on improving emotional understanding.
For the study, which appeared in Journal of Population Therapeutics and Clinical Pharmacology, researchers assessed 56 children with FASD, ages 6 to 13, for their emotional understanding. As defined by psychologists, emotional understanding means knowing how emotional processes work both in one’s self and in other people. This includes understanding the causes and consequences of emotions, as well as knowing how to regulate and cope with one’s feelings.
How are long strands of DNA packed into tiny cells?
Scientists from the Department of Biochemistry and Biophysics working with colleagues in France and Japan have described the first step of how 3 feet of DNA is packed into every cell in the body.
They have provided the first-ever detailed picture of the most basic building block of chromosomes, known as the nucleosome, and have found that a protein known as H1 (for linker histone H1) helps DNA become more compact and rigid within the nucleosome. In contrast, when H1 isn’t present, the DNA is loose and flexible.
The tight structure that H1 creates helps shield DNA from various factors that can activate or “turn on” certain genes. Without H1, DNA is more accessible to factors that could trigger disease-causing genes.
Published in the journal Molecular Cell,this finding will inform research on all processes that involve chromosomes, such as gene expression and DNA repair, which are critical to the understanding of diseases such as cancer, according to Jeffrey J. Hayes, senior study author and the Shohei Koide Professor and chair of the Department of Biochemistry and Biophysics.
The teams in France and Japan used specialized microscopes and X-rays to capture pictures of DNA molecules interacting with H1 and other key proteins. Because of the size of the DNA and protein molecules, the pictures generated by these techniques were fuzzy and difficult to analyze.
Lead study author Amber Cutter, a graduate student in Hayes’ lab, put all of the components – DNA, H1, and other proteins – together in tiny test tubes and conducted various biochemical experiments. Her tests, coupled with the X-ray images, confirmed H1’s role.
Racial disparities persist in hospital readmissions
Medicare Advantage is designed to more effectively manage health care and control costs. And yet, according to a new study in Health Affairs, black patients enrolled in the program are far more likely to be readmitted to the hospital after a surgery than those enrolled on traditional Medicare. Furthermore, significant disparities continue to exist in readmission rate between black and white Medicare patients.
“Our findings suggest that the risk-reduction strategies adopted by Medicare Advantage plans have not succeeded in lowering the markedly higher rates of readmission for black patients compared to white patients,” said Yue Li, an associate professor of public health sciences and lead author of the study. “More research will be needed to understand which managed care approaches may be effective in reducing 30-day re-admissions for white and black beneficiaries, and why existing Medicare Advantage plans do not seem to be successful in reducing racial disparities.”
In 2015 approximately 30 percent of Medicare beneficiaries (or 16 million people in the U.S.) were enrolled in private Medicare Advantage plans. Private insurers have a tremendous incentive to create programs that help patients better manage their care and reduce hospital use.
Using a database compiled by the State of New York, the authors of the study examined 30-day hospital readmission for individuals over the age of 65 for six major surgeries and found that black patients on traditional Medicare were 33 percent more likely to be readmitted after a surgery than whites. More strikingly, black patients enrolled in Medicare Advantage plans were 64 percent more likely to be readmitted.
The authors speculate that several factors may be behind this disparity, such as:
lower quality surgical care,
poorer support and follow-up care when a patient leaves the hospital,
less social and community support.
They also suggest that limitations on the choice of providers that many managed care plans impose on patients may have a disproportionate impact on black patients.
Solan, Saeed receive KL2 Mentored Career Development awards
Lauren Solan, an assistant professor of pediatrics, and Fahad Saeed, assistant professor of nephrology, are recipients of KL2 Mentored Career Development awards. The program, sponsored by the Clinical and Translational Science Institute, provides 2 years of support for new investigators interested in a career in clinical or translational research.
Solan, who is also a pediatric hospitalist at Golisano Children’s Hospital, will investigate the development of a novel pediatric risk assessment tool to predict which pediatric patients are at highest risk for unplanned readmission or Emergency Department revisit and may need additional support or resources after hospital discharge.
The Medical Center recently created a readmission risk assessment tool for adults that is built into eRecord and applied to pediatric patients, though it has not been evaluated for use in the pediatric population. Solan will evaluate the utility of the existing adult-based risk assessment tool for use in children and will modify it to address additional factors that may contribute to a pediatric patient’s risk of unplanned healthcare reutilization.
Saeed will conduct a pilot study evaluating early palliative care for elderly patients with chronic kidney disease (CKD).
CKD affects more than 20 million Americans. Elderly CKD patients are the largest growing patient population initiating dialysis in the U.S., but dialysis may be of little value to these patients. CKD patients over 75 years of age have significant symptom burden and co-morbidities, and a median survival of just 2.5 years. Many elderly CKD patients start dialysis with little knowledge of their prognosis or the impact of dialysis on quality of life, survival, and function. Currently, no proven interventions exist to help vulnerable elderly CKD patients with dialysis-related decision making, quality of life, and advance care planning.
The KL2 award will allow Saeed to investigate the impact of palliative care consultation on decision-making, disease management outcomes, and quality of life for CKD patients and their caregivers when facing decisions regarding renal replacement therapy.
Register by Sept. 1 for Early Stage Faculty Boot Camp
The boot camp, which will be held from 9 a.m. to 5 p.m. September 25 to 29, is designed to help senior instructors and assistant professors identify the skills they need for successful career advancement.
Course content includes: exploration of the myriad of local resources, sources of support for early career endeavors, mentorship, discussions with local experts including journal editors and successful individuals pursuing different career paths, work-life balance, the NIH review process, and resources for educators.
Visit the CTSI website for more details. Participants are asked to commit to all sessions. There is no charge for Medical Center faculty members. The registrationdeadline is September 1. Read more at the CTSI Stories Blog.
Fulbright opportunities in the Western Hemisphere
Opportunities abound for academics and professionals to engage in original research and teaching activities in Canada, Latin America, and the Caribbean through the Fulbright Scholar Program. Most countries in the Western Hemispherewelcome applications from any field of study and offer broad and flexible opportunities.
Brent Plansinis, Optics, “Applications of Space-time Duality.” June 30, 2017. Advisor: Govind Agrawal.
Laura Kinnischtzke, Physics, “Quantum Dot Photonics.” June 30, 2017. Advisor: Nick Vamivakas.
Daniela Geba, Translational Biomedical Science, “Utilization of Screening Methods for Type 2 Diabetes Mellitus in Primary Care Settings: Current Practices and Future Directions.” July 6, 2017. Advisor: Ann M. Dozier.
Douglas Tusch, Chemistry, “Part I. Studies Towards the Total Synthesis of (-)-Apoptolidin A. Part II. Hydroxymethylation of Aldehydes and Its Application to (-)-Rasfonin.” 1:30 p.m., July 12, 2017. 473 Hutchison Hall. Advisor: Robert Boeckman Jr.
Matthew Cavanaugh, Neuroscience, “Properties of Training-induced Visual Recovery in Cortical Blindness.” 1 p.m. July 17, 2017. Adolph Auditorium (1-7619, Medical Center). Advisor: Krystel Huxlin.
John O’Donnell, Neurobiology and Anatomy, “Extracellular Ions and Volume Regulation in Brain States.” 2 p.m. July 17, 2017. Auditorium K-307 (3-6408 Medical Center). Advisor: Maiken Nedergaard.
Christina E. Brule, Biochemistry, “Specific Codon Pairs Inhibit Translation in Yeast and Act by Distinct Mechanisms.” 2 p.m. July 20, 2017. Neuman Room (1-6823 Medical Center). Advisor: Elizabeth J. Grayhack.
Timmy Li, Epidemiology, “The Association between Neighborhood Socioeconomic Status and Disparities in Emergency Medical Services Use and Quality of Emergency Stroke Care.” 1 p.m. July 21, 2017. Helen Wood Hall 1W-501. Advisor: David Rich.
Margaret Hill, Genetics, “The Origin of Intrahepatic Cholangiocarcinoma and the Importance of MCL-1 for Tumor Development.” 10 a.m., July 24, 2017. Ryan Case Method Room (1-9576, Medical Center). Advisor: Aram Hezel.
Mark your calendar
July 14: UNYTE scientific session, “Collaborate to Innovate Maternal & Child Health Translational Research.” 10 a.m. to 3:30 p.m. Helen Wood Hall. Panel presentations, a poster session, interactive break-out groups, and a keynote address by Michele Caggana, deputy director of genetics and director of newborn screening at the Wadsworth School of Laboratory Sciences. For additional information and registration, go to UNYTE Scientific Session.
July 18:Clinical and Translational Science Institute Town Hall Meeting. Updates on new initiatives and funding opportunities; open forum question and answer period. Refreshments served. 4 to 5 p.m. Evarts Lounge, Helen Wood Hall.
July 19: Science, Technology, and Culture – a multidisciplinary reading group examining how science is shaped by the culture that surrounds it and how technological innovations change society. Join us for snacks and good conversation about Archangel, by Andrea Barrett. 5 p.m., Humanities Center Lobby (Rush Rhees Library). August book is Hidden Figures by Margot Lee Shetterly (meeting date tba). Please contact Emma_Grygotis@urmc.rochester.edu with any questions.
Sept. 25 to 29: Early Stage Faculty Boot Camp to help senior instructors and assistant professors identify the skills they need for successful career advancement. 9 a.m. to 5 p.m. Visit the CTSI website for more details. Registrationdeadline is September 1.