Kalsotra Awarded Nationally Competitive March of Dimes Research Grant
Assistant professor of biochemistry and medical biochemistry, Auinash Kalsotra, has been awarded the Basil O’Conner Starter Scholar Research Award from the March of Dimes. Created in 1973 and named for the first March of Dimes chairman and president, this program provides funding to young investigators to start their own research projects on topics related to the March of Dimes mission. The grant provides $150,000 over a two-year period for research on alternative splicing’s role in Myotonic Dystrophy, a multi-systemic disease that affects about 1 in 8000 people.
Alternative splicing is a key mechanism that produces precise assortment of proteins for each cell type. It is a highly regulated process, which when gone awry results in diseases like myotonic dystrophy type 1 (DM1). DM1 arises due to an unusual mutation where a small DNA segment of the mutated gene is repeated hundreds of times. When the mutated gene is copied into RNA, it gets trapped inside the nucleus and becomes toxic by disrupting function of muscleblind like (Mbnl) family of splicing regulatory factors. Mbnl proteins normally participate in regulation of developmental splicing transitions. Their inactivation in DM1 results in expression of embryonic splicing patterns, which is detrimental to the function of adult tissues.
While the role of Mbnl1 in DM1 skeletal and cardiac muscle pathology is clear, the effects of its loss of activity in the gastro-intestinal and other tissues are poorly understood. Dr. Kalsotra's project aims to characterize Mbnl1 function in the liver by identifying its RNA targets and determining the consequences of its loss on liver physiology and function. These studies will advance our understanding of Mbnl1 function in liver development and provide new insights into DM1 pathophysiology.
The mission of the March of Dimes is to promote healthy pregnancies and to support research that can lead to the prevention of birth defects. Dr. Kalsotra’s research will lead to our understanding of molecular mechanisms that may be responsible for the developmental defects observed in this debilitating disease. Dr. Kalsotra holds appointments in both the College of Medicine and the School of Molecular and Cellular Biology at the University of Illinois at Urbana-Champaign.
Posted February 19, 2014
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MicroRNA misregulation in muscular dystrophy
Assistant Professor of Biochemistry, Auinash Kalsotra, and colleagues have discovered the process by which myotonic dystrophy affects activity of the small bits of genetic material called microRNAs in the heart. Cardiovascular dysfunctions are the second leading cause of death in people with this particular type of muscular dystrophy. Their findings were published in the journal Cell Reports on January 9, 2014.
According to Dr. Kalsotra, myotonic dystrophy is a multi-systemic disease that affects about 1 in 8000 people. It occurs because of a change in a gene that is important for muscles. (Specifically, it is a trinucleotide repeat expansion in the dystrophia myotonica-protein kinase gene.) While most myotonic dystrophy research has focused on problems related to types of messenger RNAs produced from our genes by altered RNA splicing, this study demonstrates additional problems with expression of a class of regulatory RNAs known as microRNAs.
Dr. Kalsotra has appointments in both the College of Medicine and the School of Molecular and Cellular Biology at the University of Illinois at Urbana-Champaign.
Assistant Professor of MIP Sayee Anakk Publishes New Study in Cell Reports
Assistant Professor of Molecular and Integrative Physiology Sayeepriyadarshini Anakk published an article in the November 21, 2013, edition of Cell Reports entitled "Bile Acids Activate YAP to Promote Liver Carcinogenesis."
The article elucidates some of the ways elevated levels of bile acids cause liver cell carcinomas, including through the loss of the nuclear receptors FXR and SHP, as well as the activation of the Yes-associated Protein (YAP) of the Hippo pathway.
The MCB Communications Office also produced its first video abstract for the article.
MCB Junior Receives ASM Undergraduate Research Fellowship
The American Society for Microbiology (ASM) has selected MCB Honors student Michaela Eickhoff as a 2013 award recipient of the ASM Undergraduate Research Fellowship. This fellowship is aimed at highly competitive students who wish to pursue graduate careers (Ph.D. or M.D./Ph.D.) in microbiology. Fellows have the opportunity to conduct full time summer research at their institution with an ASM mentor and present their research results at the 114th ASM General Meeting in Boston, MA if their abstract is accepted. Each fellow receives up to a $4,000 stipend, a two-year ASM student membership, and funding for travel expenses to the ASM Capstone Institute and 114th ASM General Meeting. Ms. Eickoff works in the lab of Professor of Microbiology James Slaugh.
Posted November 20, 2013
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MCB Undergrad and Staff Writer Wins Science Journalism Student Award
MCB senior and Communications Office writer Chelsey Coombs has won the Society of Neuroscience 2013 Science Journalism Student Award. The award includes a stipend and financial assistance attending Neuroscience 2013. Coombs is also a University of Illinois News Bureau Life Sciences Intern, a Researcher in Dr. Gene Robinson's Honey Bee Laboratory, and SPIN Fellow at the National Center for Supercomputing Applications.
Posted October 25, 2013
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Researcher in Newmark Laboratory Wins Bioart Contest
Bo Wang, a post-doctoral researcher, is one of twelve winners of the NIH's BioArt Contest. Wang works in the laboratory of Professor of Cell and Developmental Biology Phil Newmark.
Read a post about Wang's image on the NIH Director's Blog.
Posted October 24, 2013
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Susan Martinis Named as a 2013 University Scholar
The Office of the Vice President of Academic Affairs recognized Professor and Head of Biochemistry Susan Martinis as one of six University Scholars at the Urbana-Champaign campus for 2013.
Martinis researches the interactions of RNA and proteins, specifically focusing on aminoacyl-tRNA synthetases. This family of enzymes accurately attaches an amino acid to its compatible tRNA molecule. A ribosome can then transfer the amino acid from this "charged" aminoacyl-tRNA molecule to a growing peptide chain. These enzymes are crucial in ensuring sequence fidelity between DNA sequences and the proteins they encode.
The University Scholars Program began in 1985 to identify "the most talented faculty members from many different disciplines" and "encourage continued professional growth and contributions to the University and the public it serves." University Scholars receive $10,000 for each of three years for career enhancement.
Posted September 12, 2013
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"Photosynthesis Research" Dedicates Article Series to Govindjee
The journal "Photosynthesis Research" announced the publication of a series of articles in honor of Emeritus Professor of Biochemistry Govindjee's contributions to photosynthesis research and education.
Govindjee has authored or co-authored over 400 publications about the details of photosynthesis and has served as a research collaborator, lecturer and editor. In the editorial announcing the special issues, Govindjee was called "the de facto Ambassador of Photosynthesis to the rest of the world."
Nearly 250 authors, representing 30 countries, contributed over 60 papers for these special issues, crafting their reviews to educate field novices and teachers of photosynthesis, as well as researchers looking for quick updates on the newest photosynthesis research.
Special issues on Photosynthesis Education honoring Govindjee Editorial
Posted September 12, 2013
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College of Medicine Recognizes Byron Kemper, Abigail Salyers for Excellence
The College of Medicine at Illinois recognized Emeritus Professor of Molecular and Integrative Physiology Byron Kemper and Arends Professor Emerita of Microbiology Abigail A. Salyers for their excellence in research and teaching.
Kemper has published over 100 papers about cytochromes P450, a superfamily of enzymes that catalyze the oxidative metabolism of many compounds and play important roles as activators and inactivators of drugs and carcinogens. He currently studies the role of nuclear receptors in the regulation of liver metabolism with his wife, Associate Professor of Molecular and Integrative Physiology Jongsook Kim Kemper. Kemper has taught physiology, cell biology, and ethics courses in the School of Molecular and Cellular Biology and has also served as the Head of the Department of Molecular and Integrative Physiology.
Salyers has published over 150 papers about the normally occurring bacteria of the human intestinal tract, which can cause infection after surgery and have become antibiotic-resistant over time. She received the G. William Arends endowed appointment in 2004 for her research achievements. Salyers has served on multiple federal advisory panels and as the President of the American Society for Microbiology. She has also been recognized for her valuable instruction to students, being awarded the Golden Apple Award, as well as appearing on the List of Teachers Ranked as Excellent by Their Students.
Honoring Dr. Abigail A. Salyers, Arends Professor Emerita of Microbiology in the College of Medicine
Honoring Byron Kemper, Professor Emeritus of Pharmacology, Molecular and Integrative Physiology, and Cellular and Structural Biology
Posted September 10, 2013
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Auinash Kalsotra Nominated for Searle Scholars Program
Congratulations to Auinash Kalsotra for his latest honor: a campus nomination for the prestigious Searle Scholars Program. Dr. Kalsotra is a member of the departments of Medical Biochemistry and Biochemistry in the College of Medicine and the School of Molecular and Cellular Biology, respectively. He recently received a Roy J. Carver Trust grant for his research on patterns in RNA splicing that determine the way liver cells naturally regenerate healthy cells across the life span.
Two scholars from the University of Illinois at Urbana-Champaign were nominated for this competitive award. The Searle Scholars Program generally selects 15 outstanding young scientists among a national pool of nominees from invited institutions. Grants are $300,000 for a three-year term. Final selections will be announced in April 2014.
Dr. Kalsotra’s research aims to shed light on possible interventions that could ultimately help people with chronic liver disease, such as hepatitis or liver cancer, to improve the body’s natural ability to regenerate healthy cells.
Posted August 23, 2013
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New MCB Web Site
On Wednesday, August 21 the MCB Web Site was completely replaced. Please report any concerns to email@example.com.
Posted August 21, 2013
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New MCB Faculty Interviews
New interviews with K V Prasanth, Auinash Kalsotra, Jim Slauch, Mary Schuler, Martha Gillette, Raven Huang, Claudio Grosman and Gary Olsen are available online.
Assistant Professor Auinash Kalsotra Awarded Two-Year Roy J. Carver Trust Grant
Congratulations to Assistant Professor of Biochemistry Auinash Kalsotra, who was recently awarded a two-year grant to study the functional role of RNA processing, a cellular process that, among other roles, regulates liver regeneration. Dr. Kalsotra is a member of the Departments of Biochemistry and Medical Biochemistry, and will be teaching first-year medical students.
Dr. Kalsotra’s laboratory, in collaboration with Dr. Sayee Anakk, assistant professor of medical molecular and integrative physiology, has identified patterns in RNA splicing that determine the way liver cells naturally regenerate healthy cells across the life span. The Carver Trust grant will fund research to understand how splicing in diseased liver cells deviates from the typical patterns, specifically focusing on how alternative splicing functions in promoting cellular repair and regeneration.
Dr. Kalsotra’s research aims to shed light on possible interventions that could ultimately help people with chronic liver disease, such as hepatitis or liver cancer, to improve the body’s natural ability to regenerate healthy cells—a process that is impeded in a diseased organ.
The Roy J. Carver Charitable Trust supports advanced scientific research to improve human health. Applicants from the fields of medicine, engineering, and the natural sciences compete regionally for large, multiyear grants.
This funding will build on current work supported by the American Heart Association, which examines how changes in alternative splicing facilitate the growth of the heart after birth.
Posted August 03, 2013
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Ning Sun Receives Baxter Young Investigator Award
Biochemistry Ph.D. student Ning Sun (Huimin Zhao Lab) was selected to receive a Baxter Young Investigator Award. Baxter Young Investigator Award Committee Member Judith L. Reinboldt says of the many nominations this year, that Sun's research "stood out as an example of innovative research," and is "not only challenging, but has potential application to critical care therapies and may lead to life sustaining therapies."
Posted August 02, 2013
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Daniel Llano Selected as Pew Scholars Nominee
Congratulations to Assistant Professor of Molecular and Integrative Physiology and the College of Medicine, and Carle Foundation Hospital neurologist Daniel Llano, who has been selected as the Urbana campus nominee for the 2014 Pew Scholars Program in the Biomedical Sciences.
The Pew Scholars Program provides funding to young investigators of outstanding promise in science relevant to the advancement of human health. The current grant level is $240,000; $60,000 per year for a four-year period. In 2014, Pew will name the next Class of Pew Scholars.
Dr. Llano’s lab studies the mechanisms by which complex sounds, such as speech, are processed by the auditory system. His work hypothesizes that the auditory system generates internal models of the sensory world and uses these models to extract meaning from complex sensory stimuli. Dr. Llano’s research informs common health care concerns such as the hearing disorder tinnitus, the effects of aging on hearing loss, and the impact of hearing loss on brain circuitry.
Dr. Llano is also affiliated with the Beckman Institute for Advanced Science and Technology. He is the discipline coordinator and main lecturer for the Brain, Behavior and Human Development course taken by first-year medical students. An alumnus of the University of Illinois Medical Scholars Program, Dr. Llano completed his Ph.D. in Molecular and Integrative Physiology in 2000 and his M.D. in 2002.
Posted July 22, 2013
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MCB Alumni Awarded Fulbright Fellowships
Two recent MCB graduates have been offered fully funded opportunities through the U.S. student Fulbright program.
Sponsored by the U.S. Department of State, the program awards 1,900 academic grants annually to U.S. citizens for use in more than 140 nations. The combined $325 million investment by the U.S. and foreign governments generally provides full funding for round-trip travel, room and board, health insurance, and full or partial tuition.
The program seeks to promote cross-cultural interaction and mutual understanding through students’ engagement in their host communities.
Matthew Moynihan, of Naperville, Ill., will conduct an English teaching assistantship in Indonesia. He has been a conversation partner for the U. of I. Intensive Language Institute and a research assistant in the neurocognitive kinesiology laboratory. Moynihan wants to immerse himself in the Indonesian culture and broaden his cultural understanding to help his development as a teacher of health. Moynihan will attend Rocky Vista University College of Osteopathic Medicine in Colorado. He intends to practice medicine abroad.
Joseph Weber, of Litchfield, Ill., will conduct research in Sweden. He is a recipient of the James R. Beck undergraduate research award and a James Scholar research award. For the past three years, Weber has served as a research assistant in professor Bruce Fouke's geomicrobiology lab. Weber hopes that his research at the Royal Institute of Technology will help him characterize the cell-membrane proteins of the relatively novel and under-investigated organism Sulfurihydrogenibium yellostonense. Weber intends to pursue a medical degree at Loyola University in Chicago.
By trying it all, predatory sea slug learns what not to eat
Emeritus Professor of Molecular and Integrative Physiology Rhanor Gillette and colleagues have found that a type of predatory sea slug that usually isn’t picky when it comes to what it eats has more complex cognitive abilities than previously thought, allowing it to learn the warning cues of dangerous prey and thereby avoid them in the future. The research appears in the Journal of Experimental Biology.
Supriya Prasanth receives NSF Career Award
Assistant Professor of Cell and Developmental Biology Supriya Prasanth has received the National Science Foundation CAREER Award. The five-year grant, according to NSF, is "in support of junior faculty who exemplify the role of teacher-scholars through outstanding research, excellent education and the integration of education and research within the context of the mission of their organizations. Such activities should build a firm foundation for a lifetime of leadership in integrating education and research."
July 14, 2013
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School of MCB Researchers Receive Mayo Clinic/University of Illinois Alliance Funding
Three School of Molecular and Cellular Biology professors have been awarded research funding by the Mayo Clinic/University of Illinois Strategic Alliance for Technology-Based Healthcare.
In January, the Mayo-Illinois Alliance for Technology Based Healthcare sponsored a Pharmacogenomics Workshop at the Institute for Genomic Biology to spread the word about the awards, which fund collaborative projects between the institutions related to pharmacogenomics. The researchers submitted their proposals and were chosen from a highly competitive pool of applicants.
Director of the School of MCB and Department of Biochemistry Professor Stephen G. Sligar, Department of Biochemistry and Cell and Developmental Biology Professor Mary A. Schuler, and Mayo Clinic researcher Rajiv Kumar, M.D., were chosen for their project, "Genetic Patient Polymorphisms and Molecular Mechanisms of Vitamin D Metabolism." They plan to "seek the linkage between patient polymorphisms and their origins related to the structure and function of metabolic gene products," focusing on defects in cytochrome P450 mono-oxygenases involved in the synthesis and catabolism of vitamin D metabolites.
Department of Biochemistry Professor David Kranz and Mayo Clinic researcher Scott Kaufmann, M.D., were chosen for their project, "A Strategy for Rapid Analysis of Bcl2 Mutants Associated with Follicular Lymphoma." They plan to study mutations of the BCL2 gene and their effects on Bcl-2 protein-ligand binding. Mutations in this gene are correlated to the reduced survival of follicular lymphoma patients. 14,000 people in the United States are diagnosed with this type of cancer per year. Posted May 28, 2013
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Team finds mechanism linking key inflammatory marker to cancer
In a new study described in the journal Oncogene, Professor of Biochemistry Lin-Feng Chen and his team reveal how a key player in cell growth, immunity and the inflammatory response can be transformed into a primary contributor to tumor growth.
Read the full story at the University News Bureau.
See coverage on WCIA News.
The paper, “BRD4 Maintains Constitutively Active NF-kB in Cancer Cells by Binding to Acetylated RelA,” is available online.
Posted May 19, 2013
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James Morrissey Selected as 2013 Sol Sherry Distinguished Lecturer in Thrombosis
The American Heart Association’s Council on Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB) selected Department of Biochemistry Professor James H. Morrissey to give the 2013 Sol Sherry Distinguished Lecture in Thrombosis at the American Heart Association’s Scientific Sessions Annual Conference.
This lecture was created in 1990 to honor the founder of the American Heart Association’s Council on Thrombosis, Dr. Sol Sherry. Sherry realized in the 1960s that thrombosis, a disease that results in the obstruction of veins or arteries through blood clotting, was not given proper attention or study. In order to rectify the situation, Sherry led a task force of the National Academy of Science's National Research Council that instituted a national conference on thrombosis, created a book encompassing this field of research, and eventually resulted in the creation of the Council on Thrombosis.
In November, Morrissey will travel to the American Heart Association’s Scientific Sessions Annual Conference in Dallas, Texas, to present a lecture on the topic of his choice. Posted May 19, 2013
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William Metcalf Appointed As G. William Arends Professor
Department of Microbiology Professor Bill Metcalf has been appointed to the G. William Arends Professorship in Life Sciences for his accomplishments in research, education, and service.
Arends was a member of the 1939 graduating class in the University of Illinois College of Medicine. This endowed professorship, established by G. William and Clair Mae Arends, recognizes extraordinary research achievement.
A formal investiture service will be held early in the Fall 2013 semester.
May 08, 2013
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Researchers find active transporters are universally leaky
There are two main ways that molecules can cross a membrane. In passive transport, molecules are able to pass through a membrane protein called a channel (which provides a wide open pathway) to get from the high concentration side to low concentration side of the membrane. This requires no energy as the molecule flows easily down its concentration gradient. In active transport, molecules are pumped by a membrane protein called an active transporter to get from the low concentration side to the high concentration side. This process requires energy, because the molecule must be pumped across the membrane against its natural concentration gradient.
In order to do their job, active transporters use the alternative access mechanism. At first, only one side of the transporter protein is open, allowing only substrate molecules on that side of the membrane to bind to the transporter. Then, a change in the transporter's shape occurs so that first the open side closes, and then the other side of the transporter protein opens, successfully moving the substrate molecule to its destination.
The surprise is that this perfect coordination works only for the main substrate of active transporters, while small molecules such as water seem to be able to sneak through while the protein is undergoing its shape change. The research conducted by the Tajkhorshid group suggests that this is likely a universal behavior for all active membrane transporters and a result of the very large structural changes they undergo.
Researchers study membrane proteins using a tool called molecular dynamics. "All the molecules in biology have to move to do their job. While you can see a lot of nice pictures of proteins showing their structure, but that's just a frozen state," Tajkhorshid said. "In order to describe the function of a biomolecule, you have to see its motion, and molecular dynamics is a nice way to do this. The method essentially solves the Newtonian equations of motion for all the atoms in the molecule we like to study."
The computer simulations involved in molecular dynamics determine the motion of the transporters using algorithms that define how the atoms of a transporter interact with each other, how they interact with solvent, and how they interact with other molecules in the system. These rules are used to calculate the total force acting on every atom at each step of the transporter's motion.
However, challenges arise when doing these computer simulations because of the sheer number of atoms and the small time steps these simulations require.
"Atoms vibrate of a period of 10 femtoseconds [one quadrillionth of a second], so if you want to have ten snapshots nicely showing how it moves, you have to take a picture every one femtosecond to describe the natural motion of the system. Because we have to take such short time steps, calculating even a few microseconds of protein motion becomes computationally very expensive. Thanks to the power provided by the national supercomputing centers we have been able to accomplish such calculations." Tajkhorshid said.
Once these molecular dynamics simulations were up and running, members of Tajkhorshid's lab noticed something that they never expected to see: the transporters were leaking, allowing small amounts of water to pass through along with the substrate.
"Initially, I was surprised, because many people, including myself, assumed that these were perfect machines going back and forth between inward facing and outward facing states," Tajkhorshid said. "For almost two years, my students told me that there was some water passing through, and I just told them to repeat their simulations using more carefully designed setups, and that something was probably wrong with their simulations!"
With a little digging, the researchers found that some other labs had experimentally shown that some transporters did, in fact, have this leaky quality.
"What we did in this work was to propose that it's not just one particular family that has this leakiness, but all of the transporters that we have been studying in the lab. We found that in all cases, every time the protein starts to undergo those large structural changes, leaks form," Tajkhorshid said.
Tajkhorshid likens this mechanism to a scenario familiar to most pet owners.
"When you open the door for someone to come in, the door has to completely open, but that provides access to small things like a dog or a cat to get out of the house. Because transporters move so much when allowing a substrate in, these leaks form, allowing water molecules in," Tajkhorshid said.
Although Tajkhorshid doesn't believe transporter leakiness plays a physiological role in the cell, this discovery adds some interesting new knowledge to the field about transporters.
"Transporters are extremely important proteins, and we would love to understand their function and how they move. If we understand that better, then we might be able to design better, more specific drugs for transporters," Tajkhorshid said.
The lab group of Illinois professor of biochemistry Emad Tajkhorshid, pictured left to right: Giray Enkavi, Jing Li, Po-Chao Wen, Emad Tajkhorshid, and Zhijian Huang.
New Technology Helps Detect Epigenetic Changes Important to Disease
Professor of Molecular and Integrative Physiology Ann M. Nardulli and colleagues at the University of Illinois and the Mayo Clinic have created a new technique for identifying methylated DNA, a modification to our genetic material that has been shown to correlate with the disease severity and metastasis ability of various types of cancers.
Genetics has been a hot topic among biologists since Watson and Crick first discovered the structure of DNA, the molecule that encodes the information in all living things. As important as the DNA itself is, scientists are now finding that the study of epigenetics, a word that literally means “on top of genetics” and refers to additional chemical modifications to DNA, may give us clues to the causes of human diseases.
Methylation, the addition of a –CH3 group to a molecule, is one of the most highly characterized epigenetic modifications. The addition of this little group has been shown to cause changes in gene expression, and often contributes to the induction and development of certain diseases like cancer.
While the analysis of these methylation patterns may point to novel ways to diagnose and treat these diseases, the current techniques for these analyses are labor intensive and require large sample volumes of DNA for accuracy.
The researchers have now developed a single-molecule test for DNA methylation using a synthetic membrane with a hole in it, known as a nanopore, which lets only one molecule pass through it to be identified. DNA is negatively charged and is able to pass through a nanopore due to charge differences on either side of the membrane. The side of the membrane that the DNA begins on is negatively charged, which repels the similarly-charged DNA, while the side that the DNA is supposed to go to is positively charged, which attracts the DNA through the nanopore. This movement creates a characteristic electrical current reading.
The scientists were able to label methylated DNA bases with a protein called MBD1 which binds to these modified bases, while leaving unmethylated DNA bases unlabeled. Because DNA bound to the MBD1 protein has a larger diameter than the nanopore’s diameter, it will not migrate through the pore, creating a different electrical current reading than that shown when the non-methylated, unlabeled DNA passes through the nanopore. This allows scientists to differentiate non-methylated and methylated DNA simply by measuring the electrical current.
While more research and development of this test is necessary to refine the process, the future clinical applications for this technology will be invaluable. Scientists may soon be able to quantify and map the locations of the MBD-1 proteins bound to target DNA molecules, providing more information and a detection method for diseases that have a characteristic methylation pattern.
The paper, “Detection and Quantification of Methylation in DNA using Solid-State Nanopores,” appears in Scientific Reports.
Read more about the Mayo-Illinois Alliance.
Posted March 28, 2013
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