2016 MCB Convocation Address by Dr. Deborah A. Paul
Thank you Dr. Sligar for the invitation to speak at the convocation, and thank you graduates for graduating so that I could have the opportunity to come back to one of my favorite places. I’m sure that most of you are here today with friends & family that have supported you in reaching this achievement. I want to talk to you today about someone who supported me, my brother Tim.
I was the shy, introverted scientist; Tim was the extroverted, artistic type. He wrote stories and poetry, and was quite a musician – playing many different instruments, though excelling at piano. He could walk into a room full of strangers and make everyone his friend. He was younger than me, but he supported me in so many ways, for example:
1. He was my date for 10 year high school class reunion – since he knew all my friends anyway;
2. He went with me when, in my mid-twenties, I was able to buy my 1st pair of toe shoes – having taken up ballet, which I always loved, a bit late in life. He knew how much it meant to me to have achieved this, and he wanted to be there.
3. He was also one of my biggest boosters for going back to get my PhD. After I had received my Masters in Biology here at Illinois, I wanted to go on for a PhD but I didn’t know what area of science I wanted to focus on. So I took a job at Abbott working on the Development side of R & D in Diagnostics, working on tests to detect Hepatitis B infection. After working a few years, I decided what I wanted to do for a PhD and took a leave of absence from Abbott to go back to grad school – combining biochemistry, virology and immunology to study Hepatitis B. Tim was so proud, and would introduce me as “my sister who’s working on her PhD.”
A few weeks before I left for grad school, Tim ended up in the hospital. He hadn’t been feeling well, and all of the lymph nodes all over his body had become enlarged. They ran all sorts of tests, but never figured out the problem. He started feeling better and was released.
A few years passed, and I was working on finishing up my PhD when I got the call that Tim had developed Pneumocystis carinii pneumonia – a type of pneumonia typically only found in immunosuppressed people. The doctors said this was consistent with a new disease that was popping up around the country – AIDS. Two weeks in ICU and a month in the hospital later, Tim survived the pneumonia that killed the majority of AIDs patients, but a few months later he developed cancer and started chemotherapy.
As I was finishing my PhD at this time, I had to decide what I wanted to do next. They had recently discovered the virus that causes AIDS – HIV, and Abbott was one of 5 companies that was to receive viral cultures from NIH to work on tests to protect the blood supply. All my work on Hepatitis B was the perfect set up to work on HIV – and I obviously had a lot of personal reasons to want to work on this virus. So I returned to Abbott, now in the research department, to do research for diagnostics tests for HIV. Unfortunately, Tim died 1 month later; he was 28 years old.
The other people in the department had already started work on an HIV Ab test that would be used to protect blood supply. I wanted to develop a test for the virus itself, and see if it was circulating in the bloodstream – even though the prevailing school of thought was that this would not be the case. I developed an ultrasensitive immunoassay and was able to demonstrate that HIV was indeed present in the bloodstream at various times throughout the disease, and this was significant because you could then:
1. Detect initial infection, which would have been useful for Tim’s 1st hospitalization when they could not determine what was wrong with him.
2. Detect viral re-emergence - since most patients, after becoming infected, entered an asymptomatic phase; but later something would trigger the virus to begin reproducing, which was a poor prognostic indicator, usually signaling the start of AIDS related diseases.
3. Monitor therapy – initial therapies were nucleoside analogues, and you could determine if the therapy was working by watching whether the level of circulating virus declined. However, most people also eventually developed drug resistance, so through monitoring for rising viral levels, you would then know to switch to a different therapy.
Abbott also had a Pharmaceutical division, and they were using computer-assisted drug design to develop small molecules that would inhibit the active site of the viral protease. However they needed a way to know which compounds were working. So we collaborated with them – since we were growing virus in culture and monitoring our cultures with the test I developed. We looked for compounds that would kill the virus in culture but leave the human cells healthy. This led to the initial protease inhibitors that were FDA approved and marketed. Though they were not in time for Tim, they changed the tide in the war against HIV infection so that AIDS was not a death sentence but a disease you could live with.
I spent 15 more years in the lab working on HIV and Hepatitis, then moved to business-side of things – though still supporting the work on HIV and Hepatitis. Later this also included work on the next generation nucleic acid tests using PCR to detect HIV, Hepatitis and other infectious diseases.
My career success then enabled me to honor Tim’s memory and his support of me by providing support to others through endowing a chair that will reside in the School of Molecular and Cellular Biology, with a joint appointment in the new College of Medicine, in the field of Infectious Disease and Immunology, in Tim’s name. I cannot tell you how happy it makes me to be able to do this.
In closing I would like to leave you with these thoughts: Do something that means something to you; that you are passionate about. If you do that, it will, by definition, make you personally successful. When you are able to, honor the support that you have received to achieve that success by giving back – and continue the circle of support.
Now – Go do great things ! Thank you.
~~ Deborah A. Paul, Ph.D. received her Masters in Biology from the University of Illinois in 1979.
Posted June 14, 2016
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Emad Tajkhorshid receives Department of Defense Multidisciplinary University Research Initiative grant
In all, the Department of Defense awarded 23 studies a total of $162 million over the next five years for experimentation and analysis. Selected studies will benefit one of the Army Research Office, the Air Force Office of Scientific Research, or the Office of Naval Research.
“Over the past 30 years, the DoD’s MURI program has resulted in significant capabilities for our military forces and opened up entirely new lines of research,” Melissa L. Flagg, deputy assistant secretary of defense for research, said in a press release. “Examples include advances in laser frequency combs that have become the gold standard in frequency control for precision in navigation and targeting; atomic and molecular self-assembly projects that have opened new possibilities for nano-manufacturing; and the field of spintronics, which emerged from a MURI award on magnetic materials and devices research.”
Associate Professor Karen Sears Receives Two Prestigious Awards
Graduate Student and Postdoctoral Fellowships
The School, and particularly the departments and labs, are proud of the awardees' accomplishments and would like to encourage incoming students and postdoctoral scholars to apply for these opportunities.
Ruth L. Kirschstein National Research Service Award (NRSA): Fellowships aim to enrich the research training of promising predoctoral students by providing individualized, mentored research experience. Applicants must propose an integrated research plan and a dissertation research project that meet the guidelines of the participating NIH Institutes and Centers. The NRSA award provides up to 6 years of support for research and clinical training including stipends, tuition and fees, and institutional allowance. The fellowship is designed to clearly enhance the individual’s potential to develop into a productive, independent research or physician-scientist.
A Round of Applause for the School’s Current and Recent NRSA Fellows!
Waqar Arif (Biochemistry, MD/PhD), Lily Mahapatra (Biochemistry), Shannon Walsh (Biochemistry), Matthew Biehl (MIP), Robin Holland (Micro), Itamar Livnat (MIP), Bernard Slater (MIP), Daniel Harris (Biochemistry), Paven Aujla (MIP), Sumanprava Giri (CDB)
American Heart Association (AHA) Fellowships are granted to help initiate careers in cardiovascular and stroke research by providing research assistance and training. Awardees devote their time to research or activities directly related to their development into independent researchers.
Congratulations to the School’s Current AHA Fellows!
Donghyun Kim (MIP), AHA Postdoctoral Fellowship
Dennis Piehl (Biochemistry), AHA Predoctoral Fellowship
The Midwest Regional Chapter of the Society of Toxicology (MRC-SOT) provides an annual Young Investigator Award to individual research trainees in the area of the toxicological sciences. The purpose of the award is to ensure that an adequate number of highly trained scientists will be available to meet the future toxicology research needs. Young Investigator awardees will present the research at the following Annual Meeting of MRC-SOT.
Kirsten Eckstrum, from the department of Molecular and Integrative Physiology, received the 2015 Midwest RC Young Investigator Award at the 2015 Spring Meeting.
The Schlumberger Foundation Faculty for the Future Fellowship, which is awarded to women scientists and engineers from developing world to pursue postgraduate studies at leading universities worldwide. After completion of the study, individuals will return to their home countries where they will contribute to the development of science. In the 2015-2016 academic year, the Schlumberger Foundation awarded new fellowships to 155 women, and has also extended 135 existing grants.
Elizabeth Amosun, from Microbiology, received the Schlumberger Fellowship in 2015.
The Damon Runyon Research Foundation encourages all theoretical and experimental research relevant to the study of cancer including cancer causes, mechanisms, therapies and prevention. After successful completion of the fellowship, Damon Runyon Fellows are eligible to apply for the Dale F. Frey Award for Breakthrough Scientists, which provides additional support to exceptional Damon-Runyon Fellows.
Melanie Issigonis, a postdoctoral fellow in the Newmark Lab, received the Damon Runyon Cancer Research Foundation award in September of 2012.
Posted April 18, 2016
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Prevalent but Under-studied Skin Infection Focus of New Research
Shisler, together with Dr. Brian Ward from the University of Rochester, will study the molluscum contagiosum virus (MCV) in detail to identify ways to regulate its underlying proteins to formulate cures for infections and diseases such as cancer.
According to the CDC, molluscum contagiosum is an infection caused by a poxvirus (molluscum contagiosum virus; MCV). It is one of the most common skin infections in children and sexually active young adults. Despite this common infection, one major hurdle is that the virus cannot be propagated in cell culture. Most other viruses, such as herpes viruses, can be grown in cultured cells, making them easier to study. The goal of this research is to use new approaches to understand what barriers cells create to prevent virus replication.
Molluscum contagiosum (MC) is usually a benign though unsightly, mild skin disease characterized by lesions (growths) that may appear anywhere on the body. Within 6-12 months, molluscum contagiosum typically resolves without scarring but may take as long as 4 years and can be associated with stigma and the anxiety it produces.
In people with weakened immune systems (i.e., HIV-infected persons or persons being treated for cancer), these lesions can become much larger and persist indefinitely. Long-term effects include scarring and secondary infections caused by bacteria. Secondary infections may be a significant problem in immunocompromised patients, such as those with HIV/AIDS or those taking immunosuppressing drug therapies.
“Viruses are one of the most abundant microorganisms on the planet, infecting every form of life from humans to bacteria. However, these are the microbes that we understand the least. By understanding how viruses hijack the host cell, researchers can begin to answer fundamental questions about virology including how we can engineer new methods to detect and cure infectious viruses,” said Shisler.
Posted January 11, 2016
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Martha Gillette and collaborators receive two grants to study the brain
The work is facilitated by two grants that Gillette is a part of: the Emergent Behaviors of Integrated Cellular Systems (EBICS), which received $25 million in National Science Foundation (NSF) renewal funding for the next five years and the National Institute of Health (NIH) BRAIN Initiative grant which has received more than $2 million in funding over three years.
The goal of the EBICS project is to build living, multi-cellular machines to solve environmental, health, and security problems. These “biological machines” will serve as a basis to deliver drugs more effectively, function as internal diagnostic tools, or as contaminant sensors in the field. Gillette’s group focuses on developing neuronal circuits to provide sensing and processing for the biological machines (biobots).
The (NIH) Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative works towards developing tools to characterize and analyze the brain at the cell and even subcellular levels to show how individual cells and neural circuits interact with each other in time and space. Gillette currently works in Beckman’s NeuroTech Group and studies the brain’s plastic responses to experience, investigating signals that shape and wire the nervous system.
Study identifies chemical in diet that determines a honey bee’s caste
A closer look at how honey bee colonies determine which larvae will serve as workers and which will become queens reveals that a plant chemical, p-coumaric acid, plays a key role in the bees’ developmental fate.
The study, reported in the journal Science Advances, shows that broad developmental changes occur when honey bee larvae – those fated to be workers – are switched from eating royal jelly (a glandular secretion) to a diet of jelly that includes honey and beebread (a type of processed pollen).
Beebread and honey contain p-coumaric acid, but royal jelly does not. Queens feed exclusively on royal jelly. Worker bees known as nurses feed the larvae according to the needs of the hive.
Experiments revealed that ingesting p-coumaric acid pushes the honey bee larvae down a different developmental pathway from those fed only royal jelly. Some genes, about a third of the honey bee genome, are upregulated and another third are downregulated, changing the landscape of proteins available to help fight disease or develop the bees’ reproductive parts.
“Consuming the phytochemical p-coumaric acid, which is ubiquitous in beebread and honey, alters the expression of a whole suite of genes involved in caste determination,” said University of Illinois entomology professor and department head May Berenbaum, who conducted the study with research scientist Wenfu Mao and cell and developmental biology professor Mary Schuler. “For years, people have wondered what components in royal jelly lead to queen development, but what might be more important is what isn’t in royal jelly – plant chemicals that can interfere with development.”
“While previous molecular studies have provided simple snapshots of the gene transcript variations that are associated with the exposure of insects to natural and synthetic chemicals, the genomics approaches used in this study offer a significantly more complex perspective on the biochemical and physiological processes occurring in plant-insect interactions,” Schuler said.
The USDA Agricultural and Food Research Initiative supported this research.
Story by Diana Yates, Life Sciences Editor, Illinois News Bureau
Photo by Terry Harrison, U. of I. beekeeper
Ann Zielinski, MCB’s Associate Director for Business Affairs, has been awarded the SPaRC Career Achievement Award.
Coming from a research background in Plant Physiology, Biochemistry and Endocrinology, Ann began her career at Illinois in the lab of I.C. “Gunny” Gunsalus, managing his research laboratory as well as his new endeavors as Assistant Secretary General of the United Nations. Over the years, Ann’s math and financial abilities were quickly recognized and grant expenditure management was added to her responsibilities. Importantly, Ann has been responsible for MCB’s performance in audits from the University, State and Federal agencies. She serves tirelessly on campus and college level administrative committees and is the 'go-to' person for advice and strategic vision. Her long-term dedication to excellence and high standards has served the School and Campus exceedingly well. “Ms. Zielinski is clearly an outstanding asset to the Illinois research enterprise,” said Dr. Stephen Sligar, director of the School of Molecular and Cellular Biology. “Her long-term dedication to excellence and high standards has served the school and campus exceedingly well. Her service is most appropriately rewarded by receipt of the SPaRC Career Achievement Award.” Sponsored Projects and Research Compliance (SPARC) is a comprehensive working group exclusively devoted to the management and administration of sponsored projects and open to all who wish to participate. SPaRC is supported by the Office of the Assistant Vice President for Business & Finance and the Office of the Vice Chancellor for Research. SPaRC Career Achievement Awards recognize professionals who have supported the field of research administration at Illinois for a minimum of ten years and have demonstrated a significant positive impact upon the support of Illinois research administration.
Posted August 24, 2015
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Andrew Belmont: Influencing a generation of chromatin biology
As a postdoc studying chromosomal structure with David Agard and John Sedat in the late 1980s, Andrew Belmont had observed intriguing ultrastructural details in interphase nuclei. “We’d see large-scale fibers about 100 nanometers thick, and then there’d be a 10- to 30-nanometer-thick fiber looping out, which we thought might represent an active gene,” says Belmont. “However, we couldn’t rule out that these features were simply artifacts of fixation or sample preparation because we couldn’t identify the region that we were looking at.”
At the time, the only method available to identify a specific chromosomal region was in situ hybridization, in which a radioactive or fluorescently labeled nucleotide probe is annealed to complementary DNA or RNA sequences that have been denatured by chemicals or heat. The technique, first described in 1969, enabled major advances in cytogenetics and genomic mapping. But it wasn’t suited to the application Belmont had in mind.
“One of the first experiments I did in my own lab was to perform a mock in situ hybridization and then take the sample to the electron microscope. I saw the chromatin structure was completely trashed at the ultrastructural level,” recalls Belmont. His group needed a way to label specific chromatin structures in cells that also preserved DNA ultrastructure. The approach they devised was described in a 1996 paper published in JCB.
“It seemed like a crazy idea at the time, and I was concerned it wouldn’t even work.”
The paper unveiled a genetic construct containing 256 lac operator repeats that, once integrated into a cell’s DNA, could be recognized by the lac repressor protein in both fixed and living cells. The site of lac repressor binding could then be visualized by indirect immunofluorescence or via fusion to the recently discovered green fluorescent protein. In mammalian cells, a single copy of the 256 repeat construct was sufficient to identify the site of its integration, which appeared under the light microscope as a tiny dot in the cell’s nucleus. Importantly, however, amplification of the inserted repeat also granted insight into chromosomal structure.
“We showed that different amplified regions fold in characteristic patterns,” notes Belmont. These patterns corresponded to whether the tag had integrated at open versus condensed chromosome regions. “We could observe large-scale chromatin fibers under a light microscope, then take them straight to the electron microscope and identify those fibers at the ultrastructural level by immunogold staining”—thus confirming that the large-scale chromatin fibers Belmont had previously seen in fixed extracted cells actually exist in live cells.
Finally, through collaboration with Andrew Murray’s lab, the researchers showed that it was possible to insert a lac operator tag at a specific site in the yeast genome. This made it possible to follow dynamics of specific chromosomal loci in living cells.
Their approach was successful, but Belmont admits he’s amazed it even got off the ground. “I kept outlining the project to prospective graduate students and no one would bite. It seemed like a crazy idea at the time, and I was concerned it wouldn’t even work.” It wasn’t clear the lac repressor would recognize the operator motif once it was assembled on nucleosomes, or that repressor binding would be detectable by the fluorescent probes and microscope cameras then available.
“It is often the case that ideas that look good on paper totally fail when confronted with the reality of biology,” agrees Carmen Robinett, first author on the paper. “Yet at every step, things just worked.”
Belmont says the credit for that goes to Robinett. “I didn’t even own a gel box at the time we began the work. I had no experience with any kind of recombinant DNA work, but Carmen basically came to the lab as a master’s student, and planned and executed what in retrospect was a really difficult cloning project to make the lac operator repeat construct. She generated the cell lines containing amplified chromosome regions with the inserts, and even established Drosophila lines carrying the repeats. But then she had to leave the lab to start her PhD degree in Berkeley, and the project languished for a year or more before my department head, Rick Horwitz, rescued me with funding for a technician.”
Belmont actually attributes his successful tenure application to this paper and the work it enabled, which includes investigations into fundamental questions about chromatin structure and localization.
Others have found it quite useful as well. “Their proof-of-principle application was inspirational,” says former JCB Editor-in-Chief Tom Misteli. “It spawned an entire tool kit for tethering proteins to chromatin and for labeling, immobilizing and targeting chromatin regions. The system has generated insights into problems ranging from DNA repair and chromatin dynamics to gene positioning and nuclear body formation.”
Original "From the Archive" article by Caitlin Sedwick, published in JCB here.
Dr. Sligar, Director of the School of MCB, has been awarded the Herbert A. Sober Lectureship
Dr. Sligar’s lab has been exploring how to reveal the structure and function of membrane proteins through the use of nanotechnology. Membrane proteins have been historically difficult to study due to many of the current biophysical and chemical techniques applicable to soluble enzymes failing to deal with insoluble aggregates. The emergence of nanotechnology could eliminate challenges faced by researchers during the solubilization of membrane proteins and allow for the study of membrane proteins from a mechanistic perspective. In this approach, the membrane protein target is transiently solubilized with a detergent in the presence of phospholipids and an encircling amphipathic helical protein belt, termed a membrane scaffold protein (MSP). The membrane protein then finds itself in a native membrane environment and is rendered soluble via the encircling MSP belt. The lab remains committed to the widest possible dissemination of the Nanodisc technology, including materials, methods and latest data from our laboratory. The Nanodisc system is now being used by hundreds of laboratories around the world that have realized great success and further advanced the technology. The American Society for Biochemistry and Molecular Biology (ASBMB) is a nonprofit scientific and educational organization with over 12,000 members. Founded in 1906, The Society's purpose is to advance the science of biochemistry and molecular biology through publication of scientific and educational journals. Dr Sligar’s Lectureship award is given bi-annually and provides a plaque, honorarium and costs related to presenting a named lecture at the ASBMB Annual Meeting, which will be held in April. Dr. Sligar is the inventor of Nanodisc technology and currently holds the University of Illinois Swanlund Endowed Chair, the highest endowed position at the University. He is also the Director of the School of Molecular and Cellular Biology and is a professor of biochemistry, chemistry, and biophysics and computational biology and an affiliate of the Institute for Genomic Biology and the Micro and Nano Technology Laboratory. To learn more about the usage of the Nanodisc nanotechnology, visit www.BioNanoCon.com or Sligar Lab.
Dr. Supriya Prasanth's lab identifies a BEN domain-containing protein as a novel transcriptional repressor of rRNA genes, in PNAS.
Rate of ribosome biogenesis dictates protein translational capacity of cells. Ribosomal RNA (rRNA), transcribed from tandem repeat units (rDNA), forms the major component of the ribosome. Therefore, transcriptional output from rDNA directly correlates with cell growth and proliferation and is often upregulated in several cancers.
Several mechanisms ensure controlled transcriptional output from rRNA genes. Transcriptional repression of a subset of rRNA genes is essential to maintain equilibrium in ribosome abundance. The study spearheaded by Dr. Abid Khan, a postdoctoral associate from Supriya Prasanth’s laboratory, identified a BEN domain-containing protein, BEND3, as a novel transcriptional repressor of rRNA genes.
Prasanth and colleagues show that BEND3 directly binds to rDNA promoter in a sequence specific manner and induces chromatin modifications leading to a transcriptionally repressive chromatin environment. BEND3 associates with the nucleolar-remodeling complex (NoRC), a major complex known to establish and maintain rDNA heterochromatin. SUMOylated BEND3 stabilizes Tip5, the bona fide component of NoRC via association with USP21 deubiquitinase. This study provides mechanistic insights into the regulation of NoRC stability and its implication in rDNA transcriptional repression. This work is published in PNAS (USA).