Researchers at Rensselaer Polytechnic Institute Uncover Mechanism of Genetic Mutations Known To Cause Familial Alzheimer’s Disease PDF Print
Researchers at Rensselaer Polytechnic Institute Uncover Mechanism of Genetic Mutations Known To Cause Familial Alzheimer’s Disease
Thu, 2014-01-09 15:37 -- katzme

New Study Pinpoints Structural Effects of V44M and V44A Mutations

January 9, 2014

New research, led by Rensselaer Polytechnic Institute researcher Chunyu Wang, has solved one mystery in the development of Familial Alzheimer’s Disease (FAD), a genetic variant of the disease that affects a small fraction of the Alzheimer’s population. In a paper published January 6 in the journal Nature Communications, Wang and his team follow the trail of two genetic mutations – V44M and V44A – known to cause FAD, and show how the mutations lead to biochemical changes long linked to the disease.

The hallmark of FAD is the accumulation of the Amyloid Beta 42 peptide (a short chain of amino acids) in unusually high concentrations within the brain. In a healthy brain, Amyloid Beta-42 (Aβ42) and a similar peptide, Amyloid Beta-40 (Aβ40), are found in a ratio of about 1 to 9. In a brain affected by FAD, this ratio is much higher. The two peptides are nearly identical:  Aβ40 is a chain of 40 amino acids in length; Aβ42 is 42 amino acids in length. However, Aβ42 is much more toxic to neurons and plays a critical role in memory failure.

“The mutations that cause FAD lead to an increased ratio of Aβ42 over Aβ40,” said Wang, an associate professor of biological sciences within the School of Science, director of the biochemistry and biophysics graduate program, and member of the Rensselaer Center for Biotechnology and Interdisciplinary Studies, who co-wrote the paper with Wen Chan, a graduate student at Rensselaer. “That’s the biochemistry, and that has been observed by many people. But the question we asked is: how? How do the mutations lead to this increased ratio?”

There are hundreds of known genetic mutations linked to FAD, but they are all related to the processing of a large protein, the amyloid precursor protein (APP), which starts its life partially embedded in the cell membrane of brain cells, and is later cut into several pieces, one of which becomes either Aβ42 or Aβ40.

In a multi-step process, enzymes make several cuts to APP, and the location of the cuts dictates whether a resulting snippet of APP becomes Aβ42 or Aβ40. If an enzyme, γ-secretase, makes an initial cut at an amino acid within APP called Threonine 48 (T48), the remaining cuts result in Aβ42, whereas if the first cut is made at amino acid Leucine 49, the process will result in Aβ40.

Wang’s team used solution nuclear magnetic resonance spectroscopy to study the three-dimensional structure and dynamics of the transmembrane portion of APP affected by the two genetic mutations, and they discovered that the mutations cause a critical change to the T48 amino acid. That change makes it more likely that γ-secretase will prefer a cut at T48, leading to production of Aβ42, and increased concentrations of Aβ42 found in the brains of patients with FAD.

“The basic idea is that – in the mutated versions – this site, T48, becomes more open, more accessible to γ-secretase,” said Wang. “What we found is that the FAD mutation basically opens up the T-48 site, which makes it more likely for γ-secretase to produce Aβ42 peptide.”

The paper, titled “Familial Alzheimer’s mutations within APPTM increase Aβ42 production by enhancing accessibility of Ɛ-cleavage site,” is available online at: http://go.nature.com/EIkz6C.

 
Rensselaer Polytechnic Institute Partners with Icahn School of Medicine at Mount Sinai to Train Tomorrow’s Health Care and Technology Leaders PDF Print

New $5 Million Research and Technology Hub at Mount Sinai is Critical Part of New $100 Million Public-Private Partnership to Boost New York City’s Biotechnology and Entrepreneurship Sectors

December 4, 2013

Rensselaer Polytechnic Institute will strengthen its strategic partnership with the Icahn School of Medicine at Mount Sinai on the launch of the new Mount Sinai Institute of Technology (MSIT).

Announced today as part of a $100 million public-private initiative to boost biotechnology innovation in New York, MSIT aims to educate a new generation of experts and create new technologies to help address and solve the world’s most critical health-care challenges. See the full announcement at: http://bit.ly/189ZQNF

MSIT is supported by $5 million from the city of New York.

“The Mount Sinai Institute of Technology is a robust extension of our partnership with the Icahn School of Medicine,” said Rensselaer President Shirley Ann Jackson. “This research and technology hub will enable innovation and discovery in biomedical technologies, health-care analytics, and education, and will drive economic development and improved health care. Rensselaer will work closely with Mount Sinai to foster the growth of the MSIT, while expanding opportunities to build Rensselaer-driven biomedical technologies upstate.”

“We are grateful to the New York City Economic Development Corporation and the administration of Mayor Michael R. Bloomberg for their generous support in helping to make MSIT a reality,” said Dennis S. Charney, the Anne and Joel Ehrenkranz Dean of Icahn School of Medicine at Mount Sinai and executive vice president for academic affairs at the Mount Sinai Medical Center. “The city has long recognized the need to expand applied science education and to establish research facilities for these efforts. The work that we’ll carry out at the Institute – from basic research to developing medical technology and devising effective treatments – will ultimately go a long way toward helping improve patient outcomes and the quality of life for people in New York City and beyond.”

MSIT seeks to transform biomedicine through discovery and development of technology-based solutions to critical unmet health-care needs. Students and faculty will engage in academic research, product development, and active entrepreneurship in areas including Big Data, cloud computing, social networking, scientific and clinical simulation, tissue engineering, sensors, microprocessors, robotics, mechatronics, drug delivery and nanomedicine, and other areas, ultimately conferring graduate degrees in Design, Technology, and Entrepreneurship (Ph.D.) and Biomedical Informatics (M.S.).

As part of the MSIT program, which will begin in the fall of 2014, Rensselaer and Mount Sinai will collaborate on the creation of five multidisciplinary research teams. Comprised of faculty members, post-doctoral scholars, and students from both institutions, each team will be devoted to solving a specific technology problem.

This collaboration furthers the partnership between Rensselaer and Mount Sinai, which in May 2013  announced an affiliation agreement to collaborate on educational programs, research, and development of new diagnostic tools and treatments that promote human health. The affiliation leverages the expertise of Rensselaer in engineering and invention prototyping and the expertise of Mount Sinai in biomedical research and patient care to develop joint educational programs, create complementary research programs, and to seek joint research funding.

The affiliation expands the research conducted at both institutions in the areas of neuroscience and neurological diseases, genomics, imaging, orthopaedics, cancer, cardiovascular disease, and scientific and clinical targets. Funding for projects will be sought on topics including precision medicine, drug discovery, stem cell biology, robotics and robotic surgery, novel imaging techniques, cellular engineering, and computational neurobiology.

Big Data, broad data, high performance computing, data analytics, and Web science are creating a significant transformation globally in the way we make connections, make discoveries, make decisions, make products, and, ultimately, make progress. The collaboration with Mount Sinai on MSIT, under the auspices of the Rensselaer Institute for Data Exploration and Applications – or The Rensselaer IDEA, is part of the university-wide effort at Rensselaer to maximize the capabilities of these tools and technologies for the purpose of expediting scientific discovery and innovation, developing the next generation of these digital enablers, and preparing our students to succeed and lead in this new data-driven world.

For more on the alliance between Rensselaer and Mount Sinai, see: http://news.rpi.edu/luwakkey/3186

 
Chemical Engineering Expert Recognized for Seminal Contributions to Bioseparations Research and Synthetic Membrane Technology PDF Print
November 6, 2013: World-leading bioseparations expert Georges Belfort, Institute Professor and a member of the Howard P. Isermann Department of Chemical and Biological Engineering at Rensselaer Polytechnic Institute, was recently elected a fellow of the American Institute of Chemical Engineers (AIChE).

In a citation, the AIChE recognized Belfort for “seminal contributions in chemical molecular engineering, bioseparations engineering and science, and synthetic membrane technology that have been described in 200 journal papers and 22 book chapters.”

“Dr. Belfort has had a remarkable career in academia. Throughout his 35 years at Rensselaer, he has pursued the highest level of excellence in education and research, with an impact in each that reinforces the reputation of Rensselaer as one of the nation’s top universities,” said Rensselaer Provost Prabhat Hajela. “We congratulate Dr. Belfort on his election as a fellow of AIChE, an outstanding honor bestowed upon him by his peers around the world. We are extremely proud to count Dr. Belfort among the distinguished faculty of Rensselaer.”

Belfort has earned a place among the world’s most respected academic and industrial chemical engineers. Throughout his career, he has made seminal contributions in liquid-phase pressure-driven membrane-based processes, bioseparations engineering, interfacial science, protein misfolding at surfaces, and affinity separations.

The editor or co-editor of three books, Belfort has published more than 200 peer-reviewed papers and 22 book chapters. His h factor, a key metric for academic researchers that measures both productivity and the impact of published research, is greater than 40. He serves on the editorial boards of several international journals and is the international editor of the Journal of Chemical Engineering of Japan. Belfort also lectures widely in both academic and industrial settings and is an active consultant in the United States, Europe, and Japan.

The American Chemical Society (ACS) Biotechnology Division recently honored Belfort with the 2011 Alan S. Michaels Award in the Recovery of Biological Products. In 2008, the American Institute of Chemical Engineers (AIChE) named Belfort one of the “100 Chemical Engineers of the Modern Era.” Also in 2008, he received the ACS E.V. Murphree Award in Industrial and Engineering Chemistry. Other major awards given to Belfort include the AIChE Clarence Gerhold Award in Separation Science and Technology in 2000, and the ACS Award in Separation Science and Technology in 1995.

Belfort is a member of the National Academy of Engineering (NAE) and a fellow of the American Institute for Medical and Biological Engineering (AIMBE). He is co-founder and former president of the North American Membrane Society, and has twice been named a fellow of the Japanese Society for the Promotion of Science.

Last year, Belfort was elected a foreign corresponding member of the Institute of Bologna Academy of Sciences, which was created in 1690 and has grown over the centuries into one of Europe’s most renowned scientific societies. Last year, Belfort was also named a member of the International Scientific Advisory Board of the Max Planck Institute for Dynamics of Complex Technical Systems. It is a six-year appointment, and the institute is one of 80 that make up the distinguished Max Planck Society for the Advancement of Science, an independent nonprofit research organization funded by the German government and named for the physicist who discovered quantum physics.

Belfort received his bachelor’s degree in chemical engineering from the University of Cape Town in South Africa, and his master’s and doctoral degrees in chemical engineering from the University of California at Irvine.

For more information on Belfort and his research at Rensselaer, visit:

  • Rensselaer Professor Georges Belfort Named to Scientific Advisory Board of Max Planck Institute, Elected Member of Institute of Bologna Academy of Sciences
    http://news.rpi.edu/luwakkey/3031
 
Nuclear Magnetic Resonance Symposium PDF Print

The Nuclear Magnetic Resonance (NMR) Core within the Center for Biotechnology and Interdisciplinary Studies (CBIS) will host the 13th Upstate New York NMR Symposium on Friday, Nov. 8, from 8:30 a.m. to 4 p.m. in the CBIS auditorium. The event is free and the Rensselaer community is encouraged to attend. Registration is requested.

Scott McCallum, director of the Nuclear Magnetic Resonance Core, who is co-organizing the symposium with Chunyu Wang, associate professor of biology and director of the biochemistry and biophysics graduate program, said the symposium should be of interest to researchers who are interested in NMR of biomolecules and structural biology.

“Nuclear magnetic resonance is a technique to probe biomolecular structure and dynamics with atomic level resolution,” McCallum said. “This is a key technique in looking at the structural basis of a number of disease states, such as Alzheimer’s disease, as well as in drug discovery and protein engineering. This will be a one-day event with a dozen speakers and I think we can expect the discussions to be quite informative.”

Featured speakers for the event are Angela Gronenborn and Lewis Kay. Gronenborn is head of the department of structural biology at the University of Pittsburgh School of Medicine, a member of the National Academy of Sciences, and an expert in the structural basis of cellular interactions. Lewis Kay, professor of biochemistry at the University of Toronto, is a leading expert in the development of NMR techniques for studying macromolecular structure and dynamics.

The symposium will also include several local speakers, including researchers from Rensselaer, the Wadsworth Center, Cornell University, Brown University, the University of Rochester, and the University of Connecticut Health Center.

Organizers request that guests register in advance by sending an email with the name of attendees, and titles of any posters to be presented, to This e-mail address is being protected from spambots. You need JavaScript enabled to view it .

 
Biotech Safety Awareness Week 2013 PDF Print

Rensselaer Polytechnic Institute
CENTER FOR BIOTECHNOLOGY AND INTERDISCIPLINARY STUDIES

Biotech Safety Awareness Week 2013 - Monday October 28th – Thursday October 31st

To underscore and support the critical importance of laboratory safety within the CBIS, a diverse array of events will be open to all RPI students, faculty and staff during the week of Monday October 28th. These lectures, exhibits and discussions will focus on several topics that are essential to the safe and compliant performance of laboratory research activities on our campus. These events are supported by the CBIS Administration, RPI Public Safety, RPI Student Health and RPI Environmental Health and Safety.

Monday 10-28-13

10:00AM – CBIS Auditorium · Assistant Chief James Hughes and Capt. Daniel McIntyre, Troy Fire Department – “Chemical and hazardous substance safety and emergency responses”; What is important to responders when there is an emergency in CBIS?

11:00AM – CBIS area (to be determined) · TFD Hazmat truck and equipment display

1:00PM – CBIS atrium and 2nd floor main lab · EH&S displays and safety shower demonstrations

2:00PM – 3:00PM – Bruggeman Room · EH&S Lab Safety Training that includes new OSHA requirements – will be required for everyone by Dec. 1, 2013

Tuesday 10-29-13

9:00AM – CBIS atrium and 3rd floor main lab · EH&S displays and safety shower demonstrations

11:00AM – 1:00PM – CBIS atrium · Safety product exhibits (Krackeler)

4:00PM – CBIS Auditorium · Ronald Musto, M.D. – “Occupational Health Issues in Biotechnology Research”

Wednesday 10-30-13

9:00AM – CBIS Auditorium · Dave Jordan, RPI Public Safety Officer – “Student lab emergencies; basic first aid and CPR”

9:45AM – CBIS atrium · Officer Jordan reviews use of the wall-mounted Automatic External Defibrillator (AED)

11:00AM - 1:00PM – CBIS atrium · Vendor Fair, including dedicated VWR safety product displays

Thursday 10-31-13

10:00AM - CBIS atrium and 4th floor main lab · EH&S displays and safety shower demonstrations

Noon – 1:00PM – Bruggeman Room · EH&S Lab Safety Training that includes new OSHA requirements – will be required for everyone by Dec. 1, 2013

3:00PM – CBIS Auditorium · Leslie Lawrence, M.D., Medical Director, Student Health – “Influenza and vaccination; student health and emergency topics”

Friday 11-01-13

11:00AM - ECAV (East campus) · flu vaccinations available for all faculty and staff

 
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