Blanchette and Scalera et al., discover new insights into an intercellular communication method in neurons

Fruit fly neuron (magenta) with extracellular vesicle cargoes (green). Cargoes are packaged inside the neuron and, then released outside of the neuron in extracellular vesicles.

Research scientist Cassie Blanchette and Neuroscience Ph.D. student Amy Scalera, working in the Rodal lab, discovered a new mechanism of regulation of extracellular vesicles (EVs). EVs are small, membrane-bound compartments that can transfer cargoes such as DNA and proteins between cells for communication. EVs are important for normal cell-cell signaling, but they are also hijacked in neurodegenerative disease to spread toxic disease proteins to other cells. Therefore, it is crucial to understand how and where EVs are formed. Blanchette and Scalera discovered a novel method of regulation of EVs specifically at the synapses (the region of the neuron that contacts adjacent cells), using the fruit fly nervous system as an experimental model.

EVs are derived from endosomes, a network of intracellular sorting compartments that cells use to separate cargoes into different ‘packages’ with distinct inter and intracellular destinations. Blanchette and Scalera found a surprising function for the proteins that regulate endocytosis, a process in which the cell membrane buds inward, thus forming a compartment to bring cargoes to endosomes. The authors found that mutants lacking endocytic proteins lose the local pool of EV cargoes that are available for release from synapses, and instead send these cargoes for disposal elsewhere in the neuron. They hypothesized that the normal function of endocytosis  is akin to a plane circling in a holding pattern at an airport – while it waits for its time to land, it is better for the passengers to circle (between the cell membrane and endosomes), nearby their destination (release in EVs), rather than being sent to an entirely different city (a different region of the neuron). They also found that disrupting this holding pattern had consequences for the physiological functions of EV cargoes; in endocytic mutants, loss of Synaptotagmin-4, an EV cargo important for neuronal adaptability, was associated with failure of the neuron to grow in response to firing. Endocytic mutants also caused synaptic depletion of the Alzheimer’s disease associated EV cargo Amyloid Precursor Protein (APP), thus suppressing its toxicity and increasing the survival of APP-expressing flies. These discoveries raise the possibility that proteins regulating EV traffic may be targets for neurodegenerative disease therapies.

MRSEC & RTI Hosts Science Outreach to Waltham Teachers

The Brandeis Materials Research Science and Engineering Center (MRSEC) and the Brandeis Research Technology and Innovation (or MakerLab) hosted a day of science and technology outreach on November 5, 2019. In the morning and for the fifth straight year, 23 Waltham High School Science teachers participated in a professional development workshop with 15 Brandeis scientists called, “Brandeis Scientists in the Classroom.” The teams of scientists and teachers visited laboratories and developed curriculum for the scientists to make future classroom visits to the High School to increase awareness of Brandeis science and to encourage WHS students to pursue STEM careers. In the afternoon, the teams were joined by more than 60 Brandeis students, staff and members of the greater community for a public event called, “Watch:City Science and Technology Forum.” This event celebrated Waltham and Brandeis as hubs of technology and discovery and promoted as a way to connect with professionals and promote science. There were short talks about public engagement with science by Waltham High School teachers Marisa Maddox and Ellen Stanton and by Brandeis scientists, Professor Avi Rodal, Dr. Anique Olivier-Mason, Dr. Vivek Vimal, and Raul Ramos. Participants also networked with each other during the poster session (20 posters by Brandeis scientists) and explored the gallery of Brandeis contributions to the Journal of Stories in Science. The organizers’ goal was for attendees to gain new perspectives in science and technology.

The event was sponsored by the Brandeis MRSEC, Research Technology & Innovation, Library, Hassenfeld Family Innovation Center, Nova BioMedical, AstraZeneca, and the New England Journal of Medicine.




REU Students Arrive for 2016 Summer Research


Amber Jones and Susan Okrah

Alongside the more than 100 Brandeis science undergrads doing research this summer, there are 19 students who are participating in our Research Experiences for Undergraduates (REU) programs. Some students are from Brandeis, but most call universities in Kansas, Virginia, Pennsylvania, New Jersey their academic homes. Eight students are from Hampton University as part of the Partnership for Research and Education in Materials (PREM) initiative between Hampton and Brandeis. The two universities are focused on fostering interest in research science in under-represented groups of undergraduates.

The two independent REU programs were each created 6 years ago with funding from the National Science Foundation (NSF) with a goal of providing a 10-week period of intensive lab research experience to rising sophomores and juniors interested in scientific careers. Professor Susan Lovett is the director of the Cell and Molecular Visualization REU and Dr. Anique Olivier-Mason is the director of the Material Research Science and Engineering Center (MRSEC) REU.

The online application process required each student to submit a transcript, two letters of recommendation and write two essays describing their research experience (if any) and their academic and research goals. This year, 8 students are participating in the MRSEC site; 11 students are working in the Biology-based Cell and Molecular Visualization REU.

Amber Jones, who is going to be a junior at Hampton University this fall, is working in the Avi Rodal lab where she is researching how proteins can be taken on and off of cell membranes. From here, she is hoping to target specific proteins that will ultimately aid in disease research.

Amber has worked in a lab before, but believes nothing could have prepared her for her experience at Brandeis. Her REU lab work has been very involved, but she wasn’t expecting the ups and downs that are a part of lab research. The graduate students and other lab members have been supportive. She has been told “it’s okay; it’s science!”

Returning REU student, Alex Cuadros is working in the Liz Hedstrom lab, says he can go to Cell and Molecular Visualization REU coordinators Cara Pina and Laura Laranjo for assistance. They “have more experience in the lab and they tell me that things don’t always work for them. They say that ‘it’s just part of the science’.”

Nicholas Martinez, who is working in Timothy Street’s lab said, “The biggest challenge I have encountered this summer with my research is being able to do cope with disappointment. Since I am working on a defined timetable and my time here at Brandeis is limited, I want to make as much progress as possible with my research.”

Susan Okrah is working in the Seth Fraden lab this summer. She believes this experience is different from a Chemistry class at Hampton University where you are given an experiment and the results are known. In the REU program, students are given a project that is a subset of their lab’s research. Unlike school, the outcome of their research is unknown. Susan said, “We are given a direction and told to see if it works.”

Alex said that in class he has learned how to do experiments, but at Brandeis he is “doing something that has not been done before so there’s no right method.” It’s also helpful to be able to ask advice about how to approach his research and “Then you go back and you figure out how to do it. You are forced to think independently.”

During the academic year, Alex works in a Biochemistry lab at UMass Amherst. He landed the job last fall as a direct result of his 2015 REU research. How did he get the job in a very competitive environment on the large UMass campus? He presented the poster that he prepared for SciFest 2015.

The most valuable lesson learned this summer? “Resilience” said Amber. Learning to cope with the changing tides of research is important. As Susan said, “people don’t really understand what goes into research until they’re here.”

Part of the REU program involves attending journal clubs and lab meetings, but the most valuable experience of this program is simply being in a lab. Both Amber and Susan agree that anyone thinking about a career in research should go through an intensive research experience such as this. Jones noted, “I wasn’t really expecting to get this type of understanding. I really appreciate that now that I’m here.”

Both Nicholas and Alex ultimately would like to attend graduate school. For Nicholas, “being able to participate in the Cell and Molecular Visualization REU program at Brandeis has been a great opportunity for me to diversify my knowledge and skill set in scientific research prior to applying for graduate school next year. This It has been a great way for me to gain experience in a new area of research that I am interested in and to become part of a different scientific community.”

The REU students are hard at work wrapping up their research and preparing their posters for the SciFest 2016 poster session that is scheduled for Thursday, August 4.

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