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.

 

 

SciFest VII Wraps Up Summer 2017 Undergraduate Research Session

The Brandeis University Division of Science held its annual undergraduate research poster session SciFest VII on August 3, 2017, as more than one hundred student researchers presented summer’s (or last year’s) worth of independent research. We had a great audience of grad students and postdocs (many of whom were mentors), faculty, proud parents, friends, and senior administrators.

More pictures and abstract books are available at the SciFest site.

SciFest VII by numbers

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.

Learning to see

How do we learn to see? Proper visual experience during the first weeks and months of life is critical for the proper development of the visual system. But how does experience modify neural circuits so that they exhibit the proper responses to visual stimuli? Knowledge of the mechanisms by which the brain is constructed early in development should inspire new therapies for repairing the brain if it develops improperly or is damaged by disease or injury.

At the present time, it is not possible to directly view all or even most connections within a living neural circuit. Therefore, neuroscientists often build computational models to study how these circuits may be constructed and how they may change with experience. A good model allows scientists to understand how these circuits may work in principle, and offers testable predictions that can be examined in the living animal to either support or refute the model.

Undergraduate Ian Christie ’16 was interested in understanding how neural circuits in the ferret visual system become selective to visual motion. At the time of eye opening, neurons in ferret visual cortex respond to an object moving in either of two opposite directions. With about a week of visual experience, each neuron develops a preference for only one of these directions, and greatly reduces its responses to the opposite direction.

Previous models of this process posited that the primary source of the change was in the organization and pattern of inputs to the cortex. But, recent experiments from the Van Hooser lab (Roy/Osik/Ritter et al., 2016) showed that stimulating the cortex by itself was sufficient to cause the development of motion selectivity, which suggests that some changes within the cortex itself must be underlying the increase in selectivity, at least in part. Further, other experiments in the lab of former Brandeis postdoc Arianna Maffei (Griffen et al., 2012) have shown that the cortex becomes less excitable to focal stimulation over the first weeks after eye opening.

Ian constructed families of computational models that could account for both of these observations. In the model, columns of neurons in the cortex already receive input that is slightly selective for motion in one of two opposite directions, but the connections between these cortical columns are so strong that both columns respond to both directions. However, the activity that is caused by simulated visual experience activates synaptic plasticity mechanisms in the model, that served to greatly reduce the strength of these connections between the columns, allowing motion selectivity to emerge in the cortical columns. The project was supervised by faculty members Paul Miller and Stephen Van Hooser, and the results were published in Journal of Neurophysiology (Christie et al., 2017).

Future experiments will now look for evidence of weaker connectivity between cortical neurons with visual experience.

This work was supported by the “Undergraduate and Graduate Training in Computational Neuroscience” grant to Brandeis University from NIH, and by the National Eye Institute grant EY022122. It also used the Brandeis University High Performance Computing Cluster.

Brandeis’ Pioneering Science Posse Program

Photo: Mike Lovett

Samia Tamazi ’20

BrandeisNow has posted an article about the history and accomplishments of the Brandeis’ Science Posse program. Read the following excerpt or the entire article:

In June, Macareno and his posse, all Class of 2020, get off Amtrak’s Acela Express train and take a shuttle bus to Brandeis for science boot camp. On the first day, they gather in a classroom in the Abelson physics building […]

(Melissa) Kosinski-Collins, who earned a PhD at MIT, tells them college science is profoundly different from high-school science. With equal parts candor and caring, she sets high expectations, describing the intense workload. The students know that they will be held to lofty standards and that she will support them.

Later in the day, they gather around a long lab table in the Shapiro Science Center, in an area Kosinski-Collins calls Hufflepuff — a nod to one of the houses at Harry Potter’s Hogwarts School. An array of equipment is scattered before them — pipettes, balances, bottles of acetic acid (vinegar) and sodium bicarbonate (baking soda). There are also aluminum foil, Kimwipes, Scotch tape and Ziploc bags.

The students’ assignment is to build an air bag. When acetic acid combines with sodium bicarbonate, they produce carbon dioxide. The students must figure out how much of each chemical to add to fully inflate a quart-size Ziploc bag. But they also have to protect an egg placed inside the bag. This is where the foil, tape and extra bags come in. Along with the cushion of air, these items can be used to keep the egg from cracking when they drop the bag from the Science Center steps, about 15 feet above the ground.

There’s an important catch. Several months earlier, at a meeting in New York, the students got the same assignment. They also completed lab reports describing the quantities of chemicals they used and how they arranged the materials inside the bag to protect the egg. These lab reports are now handed out to different students. They have 10 minutes to repeat the earlier experiment using the reports as a guide […]

Read more at BrandeisNow

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>.

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