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.

 

 

Rosbash, Hall & Young Awarded Nobel Prize

Michael Rosbash, Nobel Laureate

Brandeis researchers Michael Rosbash, the Peter Gruber Endowed Chair in Neuroscience, and Professor Emeritus of Biology Jeffrey C. Hall have received this year’s Nobel Prize in Physiology or Medicine, together with Michael Young from The Rockefeller University,  for their pioneering work on the molecular mechanisms controlling circadian rhythm.

More about Michael

More about Jeff

More about Drosophila

 

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>.

Brandeis University and NCBI to host Genomics Hackathon in April

Brandeis University is partnering with NCBI to host a Boston-area genomics hackathon April 25-27, 2016. Two previous hackathons held at NCBI successfully integrated scientists from across the country with different skill sets to tackle challenges in RNA-seq and genomics.

The August 2015 NCBI hackathon identified gaps in usability of current RNA-seq analysis tools and in just three days created software that greatly improved ease-of-use.

The August 2015 NCBI hackathon identified gaps in usability of current RNA-seq analysis tools and in just three days created software that greatly improved ease-of-use.

NCBI hackathons identify gaps in the current state-of-the-art analysis pipelines and outline feasible solutions to bring users, especially novices, closer to understanding genomic data and analysis. This hackathon will be highly cooperative: teams of 5-6 individuals will work on non-overlapping projects and share their expertise in a collaborative way. Projects planned for this session include:

  • Network Analysis of Variants
  • Structural Variation
  • RNA-Seq
  • Streaming Data and Metadata
  • Neuroscience/Immunity
  • Command-line user-interface design

The hackathon is an exciting opportunity to meet researchers in similar fields at different institutions, learn new ways of applying your work, and work with a team to contribute original work to the genomics field. Participants are also provided with the opportunity to publish their work in a newly-created F1000 hackathon channel.

Brandeis University and NCBI invite all genomics researchers to apply and visit the NCBI announcement for more information. Participants will need to bring their own laptops to the event and have some knowledge of a scripting language (Python, PERL, Shell, etc).

Please apply by 5:00 PM March 22, 2016.

Tenure-track positions in Biology (application deadline Oct 15)

The Biology Department at Brandeis University invites applications for up to two full-time, tenure-track appointments, beginning Fall 2016, from individuals who are conducting innovative research in the broad areas of molecular and cellular biology. Junior and more senior investigators will be considered, but preference will be given to hiring at the Assistant Professor level. Areas of interest range across molecular genetics, genomics and cell biology, including topics such as RNA biology, cytoskeleton, intracellular transport, development, signal transduction, transcriptional and post-transcriptional regulation, membrane biology, and epigenetics.

The research environment at Brandeis is highly collaborative, and we seek colleagues who will complement and extend existing strengths. Brandeis offers world-class research in the setting of a small liberal-arts university. Brandeis is located 7 miles from Boston, and is part of the vibrant research community of the greater Boston area.

Brandeis recognizes that diversity in its student body, staff and faculty is important to its primary mission of providing a quality education. The search committee is therefore particularly interested in candidates who, through their research, teaching and/or service experiences, will increase Brandeis’ reputation for academic excellence and better prepare its students for a pluralistic society.

To apply, please provide the following: a cover letter, a curriculum vitae, a summary of your research accomplishments to date, including a statement of your goals for future independent research (3-page limit), up to three publications, and at least three letters of reference. Applications will be accepted only through AcademicJobsOnline at https://academicjobsonline.org/ajo/jobs/6064.

First consideration will be given to applications received by October 15, 2015. Following an initial evaluation by the search committee, finalists will be invited to visit the campus to discuss their research and to meet with faculty and students/postdocs. Additional inquiries may be directed to Leslie Griffith or to Paul Garrity.

Brandeis University is an equal opportunity employer, committed to supporting a culturally diverse intellectual community. Applications are particularly encouraged from applicants of groups underrepresented in the sciences.

Brandeis will host Gene Expression and RNA Seminar (GEARS) meeting this October

Gene Expression and RNA Seminars (GEARS) club is a monthly event that includes scientific talks on the Gene Expression, RNA and Chromatin. Every month it is held at a different institute in the Boston area.

Brandeis University will be hosting the October GEARS meeting on Thursday, October 30 in Rosenstiel 118 from 6:30 – 7.30 PM and will feature three talks from Boston area researchers.  After the talks, there will be a social hour. This event is free and all are welcome to attend.

Speakers List:

“Hijacking an editing enzyme to reveal the targets of RNA-binding proteins”
Aoife McMahon, PhD, Rosbash lab, Brandeis University

“Genome protection against transposons by the piRNA amplifier complex”
Jordi Xiol, PhD, Moazed lab, Harvard Medical School

“Linking cancer metabolism, DNA repair and epigenetics: SIRT6 provides some clues”
Raul Mostoslavsky, PhD, Associate Professor, MGH Cancer Center/Harvard Medical School/Broad Institute

GEARS Club is generously supported with the help of New England Biolabs and Cell Signaling Technology.
This event is also co-sponsored by the Brandeis Biology Office.

For more information please visit: http://www.gearsclub.org/
Facebook: facebook.com/gearsboston
Twitter @gearsclub

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