Dr. Maria Spies laboratory recently published an Proceedings of National Academy of Sciences article entitled “Tyrosine phosphorylation stimulates activity of human RAD51 recombinase through altered nucleoprotein filament dynamics.” In this article the Spies laboratory addressed the regulation of the homologous genetic recombination, an enigmatic cellular mechanism responsible for the stability of our genomes and accurate repair of the most deleterious DNA damage. They combined the tools of biochemistry, chemical biology and single-molecule biophysics to determine the mechanism by which c-ABL kinase (and its oncogenic counterpart BCR-ABL) enhances the activity of human RAD51 recombinase, which catalyzes the central step in homologous recombination. Recent PhD, Shyamal Subramanyam, was first author of this work, which was a cornerstone of his dissertation.
|Grant Young, former Biochemistry undergraduate major, received “The Ponsetti Award for Research in Orthopedics” for his summer research as a U of Iowa medical student.|
The Department of Biochemistry held their 7th Annual Retreat on August 20, 2016, in the Coralville Public Library. The retreat featured 5 faculty talks and 34 poster presentations.
It was exciting to learn about all of the science happening in the Department! Congratulations to the winners of the various contests listed below.
Graduate Student Poster Competition:
1st Place: Lalita Oonthonpan (Taylor Lab) “Elucidating structure-function relationship of the mitochondrial pyruvate carrier”
2nd Place: Will Hacker (Elcock Lab) “Modeling the E. coli nucleoid subject to experimental restraints”
3rd Place: Mark Miller (Elcock Lab) “Re-parameterization of protein force fields guided by osmotic coefficient measurements from molecular dynamics simulations”
Postdoctoral/Medical Fellows and Research Staff Poster Competition:
Shyamal Subramanyam, Postdoc (M. Spies Lab) “Tyrosine phosphyorylation stimulates activity of human RAD51 recombinase through altered nucleoprotein filament dynamcs”
Undergraduate Poster Competition:
Rick Young (Wallrath Lab) “DNA damage associated with muscular dystrophy”
X-Scientist Theme Competition:
Sarah Hengel, aka Aqua Structure Girl (ASG) with her superpowers to shrink herself to the size of a water molecule, jump into protein solutions, and with her eyes shoot X-rays at the protein of interest for structural determination
The IDT and Smith-Gehring Graduate Fellowships are awarded to three of the most meritorious second year Biochemistry graduate students based on academic and research achievements.
The 2016 IDT Graduate Fellows are Colleen Caldwell and Timothy Collingsworth:
Ms. Colleen Caldwell performed extremely well in classes during her first year in the graduate program. Work she did during her rotations is likely to earn her a contribution to research papers from two labs. Ms. Caldwell graduated cum laude with a bachelor’s degree in Biochemistry and Molecular Biology and a minor in Neuroscience from the Gustavus Adolphus College in St. Peter, MN in spring 2015. She had a brilliant undergraduate career and her application to our graduate program definitely stood out. In the laboratory of Dr. Maria Spies, she is working on a project focused on deciphering the molecular mechanism of human DNA helicase RTEL1 (regulator of telomere length). Defects in the RTEL1 helicase are associated with a broad spectrum of human diseases ranging from cancer to Crohn’s. Ms. Caldwell plans to take a full advantage of Dr. Spies’ lab expertise in DNA repair helicases and custom built single-molecule equipment to decipher the RTEL1 mechanism and to gain insights into its physiological roles outside of the telomeres. In collaboration with the X-ray crystallography core and Dr. M. Todd Washington’s lab, Ms. Caldwell will also add a structural biology component to her work on RTEL1 in definition of the association between RTEL1 helicase and the PCNA processivity clamp that integrates RTEL1 activity into cellular processes that ensure accurate replication.
Mr. Timothy Collingsworth also had an exemplary first year in the graduate program. In addition, Mr. Collingsworth’s overall positive attitude and enthusiasm stood out to us. Mr. Collingsworth, who grew up in Cedar Rapids, graduated with a bachelor’s degree in Biochemistry and minors in Computer Science and Spanish from the University of Iowa in spring 2015. Mr. Collingsworth is training in the laboratory of Dr. Michael Schnieders and is working on a project in collaboration with Dr. Michael Welsh aimed to develop computational tools to combat cystic fibrosis (CF). CF is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. In humans and pigs lacking CFTR, unchecked H+ secretion by the nongastric H+/K+ adenosine triphosphatase (ATP12A) acidifies airway surface liquid, while mice that lack CFTR express little ATP12A and secrete minimal H+. Thus, airway surface liquid in CF and non-CF mice have similar pH, suggesting that inhibiting ATP12A can reverse host defense abnormalities and treat CF in humans. The goal of Mr. Collingsworth’s project is to use computer aided molecular design to create specific inhibitors of ATP12A function.
The 2016 Smith-Gehring Graduate Fellow is Hannah Miller:
Ms. Hannah Miller performed extremely well in classes during her first year in the graduate program. Ms. Miller is the department’s first Fast Track PhD student. The Fast Track program allows for high achieving University of Iowa undergraduate students to take PhD course work during their final undergraduate year. To qualify for this program Ms. Miller participated in an extensive amount of formal research in Dr. Todd Washington’s lab and maintained an exemplary academic record. Ms. Miller stated, “I was interested in the Fast Track PhD program in Biochemistry because it is a unique opportunity to dive deeper into research at a young age. The program gives me the opportunity to join a lab with my first year, giving me a great start on my thesis project. I’m very excited to see how the program will challenge me and allow me to progress as a scientist.” Ms. Miller has joined the laboratory of Dr. Kris DeMali. She is currently working on a project aimed at understanding how cells sense and transmit externally applied forces and dissecting how this process becomes dysregulated during tumorigenesis.
Congratulations to the 2016 IDT & Smith-Gehring Graduate Fellows!
Dr. John Donelson, Professor Emeritus and former Head of Biochemistry, has been awarded the 2016 Distinguished Mentor Award. Professor Donelson has an outstanding record of mentoring trainees, faculty and staff at all levels. By his example, and with his guidance and leadership, he has influenced the lives and careers of many scientists and physicians at Iowa and beyond.
After obtaining a BS in Biophysics from Iowa State, he left the comforts of his youth by joining the American Peace Corps. He taught math, chemistry and physics in Ghana, West Africa. There, he saw firsthand the havoc wrought by infectious diseases. This motivated him to return to the US, where he attended graduate school at Cornell University. He earned his PhD in Biochemistry in 1971 for work on exonucleolytic DNA sequence determination with DNA polymerase I. He was awarded a Helen Hay Whitney fellowship to further develop DNA sequencing and phage molecular biology in Cambridge, England, with Nobel Laureate Fred Sanger. Indeed, work that John and other luminaries did with Sanger during this period contributed to Sanger’s second Nobel Prize for dideoxy sequencing of DNA. Professor Donelson continued pioneering studies in molecular biology during a brief second postdoc at Stanford University with Professor David Hogness. He was then recruited to the Department of Biochemistry at the University of Iowa as an Assistant Professor in 1974. He brought back to Iowa his worldly experiences and cutting edge molecular techniques that fueled his research program on African trypanosomes for the next 37 years.
Among his 255 publications are landmark papers such as a 1974 Cell paper with Pieter Weinsick and David Hogness on chromosome mapping in the fruit fly Drosophila, his 1980 Nature paper reporting the sequence of the yeast 2 micron plasmid, and his groundbreaking contributions to the genomics of trypanosomes in three Nature and Science papers. Twenty years after first reading Scientific American articles in Africa, he wrote a 1985 review article in the same journal on “How the African Trypanosome Changes Its Coat.”
Professor Donelson served as a research mentor of 29 PhD students and 23 postdoctoral fellows. Bruce Citron, Director, Laboratory of Molecular Biology, Professor of Molecular Medicine, USF College of Medicine states “He truly cared about his students and the graduate program and provided just the right amount of guidance – not too much and not too little.” Kent Hill, Professor, Department of Microbiology, Immunology and Molecular Genetics, UCLA reports that Professor Donelson was “always available for discussion and continuously works to identify opportunities for enriching the training experience of the people in his lab or classroom.” Dr. Shiyong Li, Associate Professor, Emory University School of Medicine, states “Professor Donelson had a remarkable ability to phrase constructive criticism in a way that was encouraging, leaving me wanting to work harder and better”. Nearly all of his trainees have gone on to prominent positions in academia and industry; many are leaders in molecular parasitology and molecular biology, thereby carrying on his legacy.
At the time of his University of Iowa retirement in 2011, Dr. Louis Miller of the National Institutes of Allergy and Infectious Diseases wrote a commendation to Dr. Donelson stating, “you were always the leader in the world in molecular biology of Trypanosomes.” In 2012, John surprised us by being offered and accepting an appointment as a visiting professor at the Federal University of Rio Grand do Norte in Brazil, where he teaches biochemistry and conducts genomic research on leishmania.
Dr. Donelson will be honored at the 2016 Distinguished Mentor Award Celebration and Lecture from 3 to 5 p.m., Thursday, Sept. 1, in 1110A MERF.
Elizabeth Boehm, a Biochemistry PhD student mentored by Dr. Todd Washington, received her PhD on August 5, 2016. Elizabeth’s thesis is entitled, ” The regulation of translesion synthesis through the binding and activation of polymerases by PCNA”. Elizabeth has accepted a position as a postdoctoral position at Harvard Medical School in Johannes Walter’s lab to study DNA replication and repair in Xenopus laevis.
Zhen Xu, a Biochemistry PhD student mentored by Dr. Ernesto Fuentes, received his PhD on August 5, 2016. Zhen’s thesis is entitled, “Auto-inhibition mechanism of the guanine nucleotide exchange factor TIAM1.” Zhen has accepted a postdoctoral position at the University of Iowa in Ernesto Fuentes’ lab.
Congrats Elizabeth and Zhen!
Dr. Maria Spies laboratory in collaboration with Dr. Ashley Spies laboratory recently published an eLife Sciences article entitled “Small-molecule inhibitors identify the RAD52-ssDNA interaction as critical for recovery from replication stress and for survival of BRCA2 deficient cells.” In this study, Hengel et al. developed a high throughput biophysical method to search through a large collection of small molecules to find those that prevent RAD52 from binding to DNA and then used the information about how the small molecules bind to RAD52 to preform further computational screening. This identified a natural compound that competes with single-stranded DNA to bind to RAD52. The activity of this molecule was then validated using biophysical methods. The methods used by Hengel et al. provide the foundation for further searches for new anticancer drugs. Future studies that employ the small molecule drugs identified so far will also help to determine exactly how RAD52 works in human cells and how it helps cancer cells to survive.
This article was Ms. Sarah Hengel’s first, first author paper. Congratulations, Sarah!
Drs. Sheila Baker and Amy Lee (Molecular Physiology & Biophysics) in collaboration with Arlene Drack (Ophthalmology & Visual Sciences) have been awarded an R21 grant from the National Eye Institute entitled “Rescue of photoreceptor synapses”. This multidisciplinary team will explore the regenerative capacity of photoreceptor synapses and develop a method for making novel retinal gene therapy vectors in an effort to create new treatments for blindness.
An image from an article by Michael Hayes (MSTP, MCB) and Dan Weeks was featured on the June cover of Open Biology. The article was entitled, “Amyloids assemble as part of recognizable structures during oogenesis in Xenopus”. Amyloids (ordered protein aggregates) are traditionally associated with pathologic conditions like Alzheimer’s and Huntington’s diseases. However, there is a growing appreciation that amyloids assemble and disassemble as part of many biologically important activities. Hayes and Weeks found that amyloids were easily detectable in the cytosol and nucleus of Xenopus oocytes. Nuclear amyloids were part of structures involved in transcription by all three RNA polymerases and in RNA processing; while cytosolic amyloids were observed with in yolk platelets and other yet to be identified structures. The cover image shows the co-localization of amyloid (green), DNA(Blue) and the nucleolar protein nucleolin (red).
Congrats Mike and Dan!
On Sunday, July 31, 2016, Professor Emeritus Rex Montgomery passed away peacefully at Oaknoll as he neared his 93rd birthday. He was with his children.
Rex was the longest serving member of the department of Biochemistry, a great leader at the University of Iowa, an outstanding carbohydrate biochemist, a devoted father and grandfather, and a wonderful human being.
Rex was a 1946 PhD from the University of Birmingham. After a short stint at the University of Minnesota, Dr. Montgomery began as an assistant professor at the University of Iowa in 1955, and became a full professor in 1963. Dr. Montgomery also served as associate dean for academic affairs in the Carver College of Medicine from 1974-1995, during which time he also held the positions of associate dean of research in the CCOM and interim vice president of research for the University.
His research and scholarly efforts had a major global impact. Two of his textbooks, described as influential and strikingly important, transformed biochemistry education. Dr. Montgomery is admired and appreciated for his remarkable impact as a teacher and mentor.
In 1974, Dr. Montgomery established a new physician assistant program at the University of Iowa, and served as its director until 1976. In the years since, graduates of this program have gone on to help myriad patients throughout the state, nation and the world.
Dr. Montgomery transitioned to emeritus status in 2006 and continued to make an impact in the department and in the field of biochemistry. In addition to his scientific contributions, he and his friends, students and colleagues supported the Department of Biochemistry and many other units on campus with generous financial support.
He will be greatly missed.