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.
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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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.”
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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Unexpected function of nucleoporin RanBP2 maintains BA homeostasis, protecting against liver toxicity.
Force triggers gene expression by stretching chromatin
How genes in our DNA are expressed into traits within a cell is a complicated mystery with many players, the main suspects being chemical. However, a new study by University of Illinois researchers and collaborators in China has demonstrated that external mechanical force can directly regulate gene expression. The study also identified the pathway that conveys the force from the outside of the cell into the nucleus.
Identifying the ways mechanical forces send signals within cells has applications not only in fundamental cell biology, but also for cancer, stem cells and regenerative medicine, said mechanical science and engineering professor Ning Wang, who led the study with cell and developmental biology professor Andrew Belmont. The researchers published their work in the journal Nature Materials.
“Each cell in your body has the same DNA, but tissues behave very differently because genes are expressed differently,” Wang said. “There is so much we don’t know about gene expression. I think this work is the beginning to unravel some of the unknowns.”
Researchers have long known that forces, both external and internal, can affect cell behavior. But the question loomed as to whether the forces themselves triggered changes in gene expression, or if the forces triggered a chemical-signaling pathway within the cell.
“Cells only have two ‘senses’ to interact with their environment,” Wang said. “They cannot see or hear, but they can ‘feel’ mechanical forces and ‘taste’ chemical signals. Many studies have detailed chemical-signaling pathways, but it’s important to understand how the mechanical forces affect the cell as well. Mechanical signaling is as important as chemical signaling, and this study shows it’s a direct pathway.”
The researchers stuck tiny magnetic beads to proteins attached to the external membranes of hamster cells. They were able to change the direction and angle of the force the beads exerted while maintaining a consistent magnitude of the force, and found that the external force directly caused regions of chromatin in the nucleus to stretch out. Chromatin is the condensed DNA and protein mixture that makes up chromosomes. Using advanced imaging techniques, the researchers found an increase in transcription of the genes in the stretched regions.
“Work extending back decades has correlated chromosome decondensation with increased gene expression, but it has been extremely difficult to distinguish cause and effect,” Belmont said. “Does gene activity cause chromatin to decondense, or does decondensation actually drive increased gene expression? Here, we saw chromatin stretching directly drive increased gene expression, which provides a mechanically based mechanism for cells to sense their environment.”
The degree of stretching and therefore gene expression varied based on the direction of the force in relation to the cell’s cytoskeleton, the internal framework of protein tubes that supports the cell.
“The actin in the cytoskeleton forms bundles. When the force is perpendicular to the bundles, it’s like plucking violin strings,” Wang said. “It’s incredibly tense, and the signal is transferred through the cytoskeleton to the nucleus and stretches the chromatin. Doing it the other way, along the string direction, there isn’t much vibration, so a force of the same magnitude has less effect. The effect gets stronger the closer the angle gets to 90 degrees.”
The researchers were able to follow the force and identify the pathway that it travels along the cytoskeleton to the chromatin in the nucleus. Knowing the pathway is important, Wang said, because researchers can now explore mechanical signaling in more detail and perhaps develop ways to harness it for gene regulation or identify targets for cancer therapies.
For example, Wang’s group has published several studies detailing the unique mechanical properties of tumor-repopulating cells – cancer cells that evade standard drug therapies and tend to slip away to metastasize in new locations. He hopes that this study opens new avenues of attack to disable tumor-repopulating cells with fewer side effects than traditional cancer treatments.
Now that they’ve detailed how forces affect stretching of the chromatin, the researchers are beginning to look at how forces affect chromatin compression and what that means for gene expression. They are also probing further into other factors regulating gene expression when the chromatin is stretched.
“When we apply these forces, why are some genes activated while some are not? We think there are factors that inhibit, so that some genes are not ready to be force-activated,” Wang said.
The National Institutes of Health supported this work.
Story by Liz Ahlberg Touchstone, News Bureau
Photo by L. Brian Stauffer
MCB Faculty Named Directors of LAS Graduate Programs
Professor Satish Nair of the Department of Biochemistry has been appointed Director of the Center for Biophysics and Quantitative Biology. Professor Nair has been serving as Interim Director since November 2015. The Center for Biophysics and Quantitative Biology serves physical and computer science students who are interested in applying their knowledge to biology, as well as students with a biological background interested in instrumentation, computation, and physical aspects of biology. The cooperation and cross-training of scientists with engineering, physical sciences, and life sciences backgrounds has infused biology with powerful technologies and exciting new paradigms. Close interactions between theory and experiments have led to fundamental advances in our understanding of the physical basis of life. Now biology is undergoing a transformation with application of modern computational methods and advanced experimental tools to solve problems of unprecedented complexity. The Center for Biophysics and Quantitative Biology is interdisciplinary, consisting of over 40 faculty members who have their home departments in Biochemistry, Physics, Chemistry, Chemical Engineering, Bioengineering, Computer Engineering, Molecular and Integrative Physiology, Cell and Developmental Biology, Microbiology, and the Medical School. The Center serves as the interface between faculty research programs in experimental biophysics and quantitative and computational biology, with common interests in elucidating the physical basis of biological phenomena. The graduate degree program of the Center offers training in all aspects of this rapidly growing area. Professor Martha Gillette of the Department of Cell and Developmental Biology has been appointed Director of the Neuroscience Program as of August 2015. The Neuroscience Program is an interdisciplinary program of study and research leading to the doctoral degree. It offers a rigorous yet flexible program designed to foster the growth of the student through research activities, close interactions with the faculty, and exposure to top neuroscientists through seminars and attendance at professional meetings. Recognizing that there are many paths to success in neuroscience, the program imposes few specific requirements. Students design their own programs leading to the Ph.D., with oversight by faculty committees ensuring appropriate depth and breadth of training. The Neuroscience Program currently has over 85 affiliated faculty from more than 20 departments, and 70 students, studying the brain from a broad range of perspectives.
Posted September 27, 2016
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Dr. Ting Fu, a recently graduated MCB doctoral student from Prof. Jongsook Kemper's lab, has received the Salk Alumni award to support her postdoctoral research at Salk Institute.
Posted October 14, 2016
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A study published in PNAS by Prof. Claudio Grosman and Dr. Gisela D. Cymes has revealed the elusive link between amino-acid sequence and charge selectivity in the superfamily of nicotinic acetylcholine receptors.
Among neurotransmitter-gated ion channels, the superfamily of pentameric ligand-gated ion channels (pLGICs) is unique in that its members display opposite permeant-ion charge selectivities despite sharing the same structural fold. Although much effort has been devoted to the identification of the mechanism underlying the cation-versus-anion selectivity of these channels, a careful analysis of past work reveals that discrepancies exist, that different explanations for the same phenomenon have often been put forth, and that no consensus view has yet been reached. Here, the authors present compelling evidence for the critical involvement of ionized side chains—whether pore-facing or buried—rather than backbone atoms and propose a mechanism whereby not only their charge sign, but also, their conformation determines charge selectivity.
Two Molecular and Integrative Physiology Graduate Students Make Final Round of Graduate College’s Research Live! Competition
The competition draws entrants from across the College, and entrants are challenged to explain their graduate work in 3 minutes with only 2 slides. Presentations were scored on delivery, clarity, effectiveness of visual material, and accessibility of language.
Ms. Mapes’ presentation titled, “What Makes Breast Cancer Cells Grow?” focuses on elucidating the mechanisms by which hormones and growth factors control normal breast development and how they are disregulated in breast cancer.
“We have discovered a novel gene, called Cuzd1, that plays an essential role in breast development and is overexpressed in a subset of human breast tumors. This research has allowed for a better understanding the specific pathways that regulate the growth of the breast and enabled us to devise more targeted therapies to treat breast cancer,” she said.
Mapes entered Research Live! “because it seemed like it would be a fun challenge, and it certainly was. It is so important for the general public to understand the research being done at institutions like the University of Illinois and events like this are a great way to get both the graduate students and the community engaged in this process.”
Jessica Saw’s presentation, “Kidney Stones: Exposing Geology Within the Human Body,” explains that even though kidney stones are extremely common, the exact mechanisms of formation are still not understood.
“I presented our hypothesis of microbially-induced formation mechanisms in the kidney stone, showing evidence in high resolution microscopy and 16S rRNA gene sequencing results. Recognizing the similarities between environmental geology and biomineralization in our body, we are applying geological technique and concepts to this interdisciplinary work,” said Saw.
Saw entered the contest “because I really identified with the Research Live! concept. I’ve been to many talks where interesting topics were ruined by poor presenting, and it really shouldn’t be that way. There is a component of performance, and even entertainment, in presenting - it is important not to neglect that!”
Watch the Research Live! Presentations:
Janelle Mapes: What Makes Breast Cancer Cells Grow?
Jessica Saw: Kidney Stones: Exposing Geology Within the Human Body.
Posted December 16, 2016
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