James Collins to receive the 2017 Gabbay Award on Oct. 18

James Collins

On Wednesday, October 18, 2017, the 2017 Jacob and Louise Gabbay Award in Biotechnology and Medicine will be given to James J. Collins from MIT. Professor Collins will be delivering his lecture entitled Synthetic Biology: Life Redesigned at 4:00pm at Brandeis in Gerstenzang 121.

Professor Collins is receiving the award “for his inventive work in synthetic biology that created a new area of research, enabling multiple biomedical applications and launching a new sector of the biotechnology industry”. He is the Termeer Professor of Medical Engineering and Science and Professor of Biological Engineering at MIT, also Core Founding Faculty at the Wyss Institute (Harvard University) and an Institute Member of the Broad Institute.

The Gabbay Award was created in 1998 by the Jacob and Louise Gabbay Foundation in order to recognize scientists working in academia, medicine or industry for their outstanding achievements developing scientific content and significant results in the biomedical sciences.

 

CaMKII: some basics to remember

The theme of Thursday’s Volen Center for Complex Systems annual retreat will be Breakthroughs in understanding the role of CaMKII in synaptic function and memory and honors the pioneering work of John Lisman. To help bring non-experts up to speed, we asked Neuroscience Ph.D. students Stephen D. Alkins and Johanna G. Flyer-Adams from the Griffith lab at Brandeis for a quick primer on CaMKII.

What’s a protein kinase? 

Protein kinases are enzymes that act by adding phosphate groups to other proteins – a process called phosphorylation. Phosphorylation of a protein usually initiates a cascade of downstream effects such as changes in the protein’s 3D shape,  changes in its interactions with other proteins, changes in its activity and changes in its localization. In causing these types of changes, kinases facilitate some of the most essential cellular and molecular processes required for survival and proper functionality.

Aren’t there lots of protein kinases? What makes CaMKII special? 

Among the roughly 500+ genes in the human genome encoding protein kinases, a kinase known as calcium (Ca2+)/calmodulin-dependent protein kinase II (CaMKII) phosphorylates serine or threonine residues in a broad array of target proteins.  Though found in many different tissues (skeletal muscle, cardiac muscle, spleen, etc.), there is a lot of CaMKII in the brain– about 1% of total forebrain protein and 2% of total hippocampal protein (in rats). Previous research, including pivotal contributions from the Lisman Lab at Brandeis University working in mammalian brain, has identified CaMKII as a cellular and molecular correlate of learning and memory through its multiple roles governing normal neuronal structure, synaptic strength, plasticity, and homeostasis. The Griffith Lab has been instrumental in demonstrating that these roles of the kinase are conserved in invertebrates.

Why do we think CaMKII might play a role in memory?

a) Location!

As previously mentioned, CaMKII accounts for up to 2% of all proteins in memory-important brain regions like the hippocampus. It’s also highly abundant at neuronal synapses, where neurons communicate with each other.

b) Function!

Memory is thought to require a process called long term potentiation (LTP) where two neurons, in response to environmental changes, will change the strength of the synaptic connections by which they communicate with each other—these changes will last even after the environmental input has disappeared. We know that CaMKII is required for LTP. We also know that the increases in neuronal calcium levels that accompany neuronal activation and cause LTP also allow CaMKII to phosphorylate itself. This autophosphorylation of CaMKII changes its kinase activity so that CaMKII can stay active well past the window of neuronal activation, essentially ‘storing’ the memory of previous neuronal activity—much like LTP!

c) Structure!

Ultimately, the issue with ‘molecular memory’ is that all proteins degrade over time, causing one to ask how we can remember things for so long when the original proteins that stored that memory no longer exist. CaMKII is such an exciting candidate for molecular memory because it is mostly found as a dodecameric holoenzyme—this means that CaMKII likes to exist as a big assembly of twelve identical CaMKII subunits. However, each CaMKII subunit retains its kinase activity even when all twelve are assembled. What’s interesting is that the autophosphorylation and activation of one CaMKII subunit (which happens when neurons are activated and intracellular calcium levels rise) actually makes it easier for the other CaMKII subunits in the twelve-unit holoenzyme to become autophosphorylated and activated. This means that maybe when an activated subunit is old and get degraded, another new CaMKII subunit could take its place among the twelve-unit holoenzyme—and become activated just like the old subunit, allowing for the ‘molecular memory’ to last beyond when proteins degrade!

CaMKII phosphorylation and activationCaMKII in more detail…

Calcium binds to the small protein calmodulin and forms (Ca2+/CaM), which acts as a ‘second messenger’ that increases in concentration when neurons are activated. CaMKII relies on calcium/calmodulin (Ca2+/CaM) binding to activate an individual domain containing a regulatory segment.  In conditions of low calcium, elements within the CaMKII regulatory segment will have less affinity for (Ca2+/CaM) binding, keeping CaMKII in an autoinhibited state.  In conditions of high calcium, (Ca2+/CaM) binding initiates phosphorylation at three threonine residue sites, including Thr286 which prevents rebinding of the regulatory segment, thus keeping CaMKII constitutively active even when calcium levels fall.  In this activated state CaMKII can autophosphorylate inactivated intra-kinase domains, and will undergo subunit exchange with neighboring inactivated CaMKII holoenzymes. Furthermore, mutation of CaMKII residues or binding sites in target proteins, such as postsynaptic glutamate (AMPA) receptors, disrupts establishment of long-term potentiation (LTP) in neurons.  Together, CaMKII’s role as molecular switch that bidirectionally, and autonomously regulates activity in neurons has earned it the illustrious title of a “memory molecule.”

What amino-acid manipulations might I hear about?

a) T286A:

Changing a threonine in a phosphorylation site to an alanine prevents phosphorylation at that site. Blocking Thr286 phosphorylation with a T286A mutation prevents CaMKII generation of autonomous activity that disrupts neuronal activity and results in learning deficits.

b) T286D:

Changing a threonine to an aspartate puts a negative charge at the site, often making it act like it’s always phosphorylated. In the case of CaMKII, a T286D mutation renders the kinase constitutively active, which can interrupt normal LTP induction and normal memory storage and acquisition.

To learn more:

Judith Tsipis Steps Down as Director of Genetic Counseling Program

Tsipis dinner

After 25 years at the helm of the Brandeis Genetic Counseling program, Judith Tsipis has handed over the leadership reins to Gretchen Schneider.

On June 3rd, close to 100 people gathered in the Levin Ballroom at Brandeis to honor and celebrate Judith’s illustrious career as a pioneer in the field of training genetic counselors. Attendees included over 40 alumni, former and present faculty members, family and close friends.

Highlights and memories were shared by: Beth Rosen-Sheidley, an alum from the first graduating class in 1994; Kathryn Spitzer Kim, the first Assistant Director from the Program; Gretchen Schneider; Judith’s son Yanni and husband, Kosta; and two additional alumni, Christa Haun and Jason Carmichael.

Judith created the master’s program in response to her own family’s experience with Canavan disease, a recessive degenerative disorder that causes progressive damage to nerve cells in the brain. Brandeis admitted its first class in 1992 and is proud to have over 200 alumni.

Judith will continue to be involved with the program in various capacities: coordinating journal club, serving as a thesis advisor and member of the Advisory Board.

 

 

 

Colleagues and Students Gather for Astrophysics Symposium

by Roopesh Ojha (PhD ’98)

Radio Galaxy NGC 4261. (credit: Teddy Cheung)

From June 28th through 30th, about fifty former and current students, colleagues and friends of Brandeis astrophysics Professors John Wardle and David Roberts gathered in the Physics building for a symposium titled “When Brandeis met Jansky: astrophysics and beyond.” This event was organized to celebrate their achievements in astrophysics and their impact on generations of students. Their work has established Brandeis as a major player in radio astronomy.

The symposium title refers to Karl Jansky who is credited with starting an entirely new means of studying the cosmos using radio waves. Radio astronomy arrived at Brandeis with Professor Wardle in 1972. He was joined in 1980 by Professor Roberts and together they pioneered a very powerful observational technique called Very Long Baseline Polarimetry. This involves the use of telescopes separated by thousands of kilometers to produce the sharpest images available to astronomers. Their methods allow astronomers to map the magnetic fields in and near celestial objects. With their students and colleagues, John and Dave have exploited this technique to study the magnetic fields in quasars and active galaxies, and near super massive black holes far outside our Milky Way galaxy as well as black holes closer to home.

Physics Conference Group

Professors John Wardle and David Roberts (front right) with former students and colleagues on the steps of the Abelson physics building (photo: Mike Lovett)

The reach of John and Dave’s work was reflected in the content of the presentations and the composition of the attendees, some of whom had traveled from as far afield as South Korea, India, and Europe. All major centers of radio astronomy were represented. At the conference dinner, several former students expressed their appreciation for the roles Dave and John have played as their mentors.

In their presentations, Dave and John described their current projects and highlighted the work of their undergraduates, graduate students and postdoctoral fellows, who have all gone on to successful careers in academia and industry.

The nineteen PhD theses produced by the Brandeis Radio Astronomy group

Professor Roberts has decided to retire at the end of August, though his retirement plans include a huge program of continuing research into unusual-shaped radio galaxies. These may represent galaxy mergers and the possible merger of their central black holes, and is being carried out with colleagues in India. Professor Wardle has no intention of retiring and is expanding his horizons so to speak — he is part of the Event Horizon Telescope collaboration, an international team of astronomers that is attempting to make the first image of the ‘event horizon’* of a black hole!

The symposium was organized by Teddy Cheung (PhD ’05, now at the Naval Research Laboratory) and Roopesh Ojha (PhD ’98, now at NASA, Goddard Space Flight Center), with generous help and support from the Physics Department.

* The boundary around a black hole beyond which nothing can escape.

Summer SciFest 2017 to Showcase Undergrad Research on August 3

SciFest 2016Brandeis Summer Scifest, an Undergraduate Research Poster Session, will be held on Thursday, August 3. The poster session will be 1:00 to 3:00 pm in the Shapiro Science Center atrium.

SciFest is an annual poster session for undergraduates who have spent their summers working in both on-campus and off-campus labs doing scientific research, usually alongside grad students, postdocs and faculty members. It an opportunity for undergraduates from across the Division of Science, including summer visitors and Brandeis students, to present posters summarizing their research.

There were 106 posters presented last year. Prospective presenters for this year should note that the deadline to register for this event is July 25. Early registrants will get the prime locations for their posters!

The public is invited to attend and to discuss research with the students. As always, refreshments will be served.

2nd Boston Symposium of Encoded Library Platforms was held Aug. 4

BSELP imageThe Brandeis Chemistry Department, together with GlaxoSmithKline and Pharmaron, is hosting the 2nd Boston Symposium of Encoded Library Platforms on August 4th in the Shapiro Theater. This symposium will feature 8 speakers from industry and academic labs, covering the newest developments in the technology of encoded small molecule libraries and related topics.

For several decades, major efforts have gone into discovering drug leads by high-throughput screening, in which “libraries” of thousands to millions of random compounds are tested in a highly repetitive fashion for biological activity, such as the ability to inhibit an enzyme. A new and elegant alternative to this process is the use of encoded libraries, in which each random molecule within the library bears a “tag” of DNA with a unique sequence. Libraries containing hundreds of millions of DNA-tagged compounds can be incubated with a target protein in a single tube, and those which bind to the target can be identified by high-throughput sequencing of the DNA barcodes in the protein-bound fraction. This approach has gained great popularity in the last few years, and is just this week the cover story of Chemical & Engineering News.

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