Rodal lab find surprising new link between inflammation and Lowe Syndrome

Could a disease with symptoms in the brain, eyes, and kidneys actually be caused by problems with immune cells? A team of scientists from the Rodal Lab, co-first authored by Steven Del Signore and Sarah Biber and including three Brandeis undergraduates (Katy Lehmann ‘16, Stephanie Heimler ‘17, and Ben Rosenfeld ’18), think this just might be the case with Lowe Syndrome, in a new paper published Oct 13th in PLOS Genetics.

Patients with Lowe Syndrome suffer from kidney failure, congenital cataracts, and several neurological problems including intellectual disability and seizures. Scientists have known for some time that the disease is caused by mutations in a gene called OCRL, but remain unsure how its loss causes such a diverse array of symptoms. A big problem has been that OCRL appears to do many different jobs inside cells, including controlling how they divide, how they sense their surroundings, and how they store and transport materials inside small packages called endosomes.

Fly immune cells showing the tracks of moving endosomes. Single tracks represent the path of individual endosomes over time.

To try to solve this mystery, a team of researchers from the Rodal lab used the fruit fly, which has its own version of the OCRL gene and allowed the investigators to perform powerful genetic experiments to figure out precisely what OCRL is doing, and where. To do this, the group created a fly missing its OCRL gene. They were surprised to find that, rather than eye or neurological defects, loss of OCRL hyper-activated cells of the innate immune system. The innate immune system is the first line of defense against infection in humans (and the only defense in fruit flies), when cells release inflammatory signals that mobilize specialized cells to attack invading pathogens.

The team determined that OCRL is required in one of these specialized immune cells in the fly, and that the immune-cell activation was caused by problems in a particular step of intracellular transport. Every cell of the body has its own postal service, which is used to pack and ship signals that tell the cell or its neighbors to grow, divide, or jump into action (see movie here to watch endosomes moving inside living fly immune cells). The OCRL mutant immune cells had a problem in a key step that controls whether signals get thrown in the trash or shipped outside the cell, and this caused the immune activation.

How do these findings relate to Lowe Syndrome? The authors think these results suggest a possible cause for the seizures that patients experience. When similar immune-like cells in the brain release excessive inflammatory signals, it can cause several forms of epilepsy. Further, OCRL has been linked to at least one mouse model of epilepsy. Going forward, the researchers will try to identify which immune signals are responsible, and how these findings translate to human cells.

Del Signore SJ (*), Biber SA (*), Lehmann KS, Heimler SR, Rosenfeld BH, Eskin TL, Sweeney ST, Rodal AA. dOCRL maintains immune cell quiescence by regulating endosomal traffic. Plos Genet. 2017;13(10):e1007052.

 

 

Searches for Tenure-Track Faculty in the Sciences, 2017

Brandeis has six open searches for tenure-track faculty in the Division of Science this fall, with the intent to strengthen cross-disciplinary studies across the sciences. We are looking forward to a busy season of intriguing seminars from candidates this winter.

  1. Assistant Professor of Biochemistry. Biochemistry is looking for a creative scientist to establish an independent research program addressing fundamental questions of biological, biochemical, or biophysical mechanism, and who will maintain a strong interest in teaching Biochemistry.
  2. Assistant Professor of Chemistry. Chemistry seeks a creative individual at the assistant professor level for a tenure-track faculty position in physical (especially theoretical/computational) chemistry, materials chemistry, or chemical biology.
  3. Assistant Professor of Computer Science. Computer Science invites applications for a full-time, tenure-track assistant professor, beginning Fall 2018, in the broad area of Machine Learning and Data Science, including but not limited to deep learning, statistical learning, large scale and cloud-based systems for data science, biologically inspired learning systems, and applications of analytics to real-world problems.
  4. Assistant Professor in Soft Matter or Biological Physics. Physics invites applications for the position of tenure-track Assistant Professor beginning in the fall of 2018 in the interdisciplinary areas of biophysics, soft condensed matter physics and biologically inspired material science.
  5. Assistant Professor or Associate Professor in Psychology. Psychology invites applications for a tenure track appointment at the rank of Assistant or Associate Professor, with a specialization in Aging, to start August 2018. They seek an individual with an active human research program in any aspect of aging, including cognitive, social, clinical and health psychology.
  6. Tenure Track Assistant Professor in Applied MathematicsMathematics invites applications for a tenure-track position in applied mathematics at the rank of assistant professor beginning fall 2018. An ideal candidate will be expected to help to build an applied mathematics program within the department, and to interact with other science faculty at Brandeis. Candidates from all areas of applied mathematics will be considered.

Brandeis University is an equal opportunity employer, committed to building a culturally diverse intellectual community, and strongly encourages applications from women and minorities.  Diversity in its student body, staff and faculty is important to Brandeis’ primary mission of providing a quality education.  The search committees are therefore particularly interested in candidates who, through their creative endeavors, teaching and/or service experiences, will increase Brandeis’ reputation for academic excellence and better prepare its students for a pluralistic society.

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.

Research Funding For Undergrads: MRSEC Summer Materials Undergraduate Research Fellowships

The Division of Science wishes to announce that, in 2017, we will offer seven MRSEC Summer  Materials Undergraduate Research Fellowships (SMURF) for Brandeis students doing undergraduate research, sponsored by the Brandeis Materials Research Science and Engineering Center.

The fellowship winners will receive $5,000 stipends (housing support is not included) to engage in an intensive and rewarding research and development program that consists of full-time research in a MRSEC lab, weekly activities (~1-2 hours/week) organized by the MRSEC Director of Education, and participation in SciFest VII on Aug 3, 2017.

The due date for applications is February 27, 2017, at 6:00 PM EST.

To apply, the application form is online and part of the Unified Application: https://goo.gl/9LcSpG (Brandeis login required).


Eligibility

Students are eligible if they will be rising Brandeis sophomores, juniors, or seniors in Summer 2017 (classes of ’18, ’19, and ’20). No prior lab experience is required. A commitment from a Brandeis MRSEC member to serve as your mentor in Summer 2017 is required though. The MRSEC faculty list is: http://www.brandeis.edu/mrsec/people/index.html

Conflicting Commitments
SMURF recipients are expected to be available to do full time laboratory research between May 30 – August 4, 2017. During that period, SMURF students are not allowed to take summer courses, work another job or participate in extensive volunteer/shadowing experiences in which they commit to being out of the lab for a significant amount of time during the summer. Additionally, students should not be paid for doing lab research during this period from other funding sources.

Application Resources
Interested students should apply online (Brandeis login required). Questions that are not answered in the online FAQ may be addressed to Steven Karel <divsci at brandeis.edu>.

How different metals stick together

Editor: Tamara Hanna JEM: Esther RTP: Bryan Nolte

Cover artwork from Inorganic Chemistry featuring paper from the Thomas group

Metal-metal interactions are at the heart of some of the most interesting metal-catalyzed transformations and are found everywhere from Nature (metalloenzymes) to industrially important heterogeneous catalysis (surfaces, nanomaterials).  While textbooks have been written about metal-metal multiple bonds, surprising gaps in knowledge remain, including bonding between first row transition metals and bonding between different metals.  The Thomas group in the Brandeis Chemistry Department seeks to fill these gaps in knowledge through the systematic synthesis of heterobimetallic complexes featuring a wide range of different transition metals and developing a thorough understanding of the electronic structure and bonding of these novel compounds.

The latest issue of Inorganic Chemistry features cover artwork highlighting the recent paper from the Thomas laboratory titled “Exploring Trends in Metal–Metal Bonding, Spectroscopic Properties, and Conformational Flexibility in a Series of Heterobimetallic Ti/M and V/M Complexes (M = Fe, Co, Ni, and Cu).” The paper describes an extensive study of a series of Ti/M and V/M heterobimetallic complexes, where M is systematically varied across the periodic table from left to right (Fe, Co, Ni, Cu).  These complexes are classified as “early/late” heterobimetallic complexes because they feature one metal from the left half of the periodic table (“early”) and one metal from the right half of the periodic table (“late”).  The inherent differences between the properties of the two metals makes their metal-metal bonding quite polar and sensitive to a variety of different factors, but also poises these compounds for interesting reactivity because of the two electronically different metal sites presented. This latest installation from the Thomas group uncovers trends in metal-metal bond distance determined using X-ray crystallography, and uses a variety of spectroscopic (EPR, NMR, Mossbauer) and computational tools to probe the electronic structure of these compounds.  Most interestingly, these compounds are shown to be conformationally flexible, with ligand rearrangements occurring rapidly in solution and this ligand hemilability, which is ideal for facilitating reactivity, can be correlated directly with the strength of metal-metal interactions.

This paper was highly collaborative and its preparation involved researchers from both Brandeis and Harvard University. The synthesis and characterization of the new compounds were largely carried out by Bing Wu, a graduate student in the Thomas group, along with Chris Thomas herself. Matt Wilding, a recent Ph.D. graduate student from the Betley laboratory at Harvard University, assisted with the collection and interpretation of Mossbauer data and designed the cover artwork. Recent Ph.D. graduate Mark Bezpalko, of the Thomas/Foxman groups, and Bruce Foxman carried out all of the structural work in the Brandeis X-ray Diffraction Facility, and all of the computational studies were carried out by Bing Wu and Chris Thomas using the Brandeis high performance cluster.

Irving Epstein has been named AAAS Fellow

irving-epstein

In recognition of his contribution to the study of oscillating chemical reactions, Irving Epstein, the Henry F. Fischbach Professor of Chemistry, has been selected as a Fellow in the American Association for the Advancement of Science (AAAS).

Epstein, who in his 45 years at Brandeis has served as Provost and Dean of the Arts and Sciences, said he was honored to receive the award from the AAAS. “I’m delighted and grateful for the recognition,” he said. “It’s always nice to be appreciated by fellow scientists.”

 

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