Virtual Conference: Climate & Math to be held 5/26/22

As part of the Brandeis’ Year of Climate ActionThomas Fai, Assistant Professor of Mathematics and Jonathan Touboul, Associate Professor or Mathematics (with Denis Patterson from Princeton University) have organized a Climate and Math Conference for Thursday, May 26th (10:00 AM to 5:00 PM). This will be a virtual one-day conference offered as part of the Brandeis Mathematical Biology Seminar.

This conference will bring together leading researchers in mathematical modeling related to climate change. It will cover techniques from mathematical modeling, data analysis and climate policy, and topics including impact of climate change on vegetation, animal populations, water/ice, carbon, and human health.

This virtual conference is part of the Brandeis Year of Climate Action program that will be occurring throughout 2022 and 2023. The Office of Sustainability is responsible for this program.

 

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.

SARS-CoV-2 Nsp14 mediates the effects of viral infection on the host cell transcriptome

SARS-CoV-2 is the pathogen causing the COVID-19 pandemic, that as of early February 2022 has caused 5.7 million deaths worldwide.

When a virus infects a cell, it transforms it, so it can become a “virus factory”. To do so, it needs to suspend it from doing the normal functions, but not to a point that the immune system will detect those changes and “decide” to kill the infected cell. Understanding how viruses accomplish that is very important for virology and medicine as, for example, it could be used to help the immune system identify these cells and stop the virus from spreading through the body.

Graphical abstract for Zaffagni post

To tackle this issue, researchers identify genes that get activated or repressed when a virus infects a cell. One way to monitor the genes that are “on” or “off” during the infection is to measure RNAs abundance by RNA sequencing (RNA-seq). Through this approach, recent studies showed that SARS-CoV-2 infection induces big changes on the cells that it infects. Generally, scientists believe changes induced by viral infection are the consequence of the concerned action of the virus proteins acting within the host cell. For example, the SARS-CoV-2 genome encodes 29 proteins. The effect of the virus is so strong that it changes more than 5000 genes in just 48hs, this is almost ¼ of our genes.

How do individual viral proteins contribute to these changes? To answer this question, the Kadener lab in the Department of Biology introduced singular viral SARS-CoV-2 proteins into human cells and monitored gene expression changes through RNA-seq. Between the 26 tested proteins, non-structural protein 14 (Nsp14) was the one inducing the most dramatic effect, altering the expression of ≈4000 genes. Importantly, these changes overlap well with previously published RNA-seq data from human cells infected with SARS-CoV-2. This suggests that transient expression of Nsp14 partially recapitulates the molecular events downstream to SARS-CoV-2 infection. They also showed that a cellular enzyme (IMPDH2) mediates these changes, and that treatment with IMPDH2 inhibitors partially rescues the changes induced by Nsp14.

This research contributes to understanding the function of viral proteins on the host cell and on the molecular mechanisms that control the progression of viral infection. The Kadener lab showed that Nsp14 also modulates gene expression of the host cell by activating a cellular enzyme. These events may be conserved in other coronaviruses infections and the discovery of these molecular mechanisms may be important for designing new therapeutic approaches.

Publication:

SARS-CoV-2 Nsp14 mediates the effects of viral infection on the host cell transcriptome. Michela Zaffagni, Jenna M Harris, Ines L Patop, Nagarjuna Reddy Pamudurti, Sinead Nguyen, Sebastian Kadener.  eLife 2022;11:e71945 DOI: 10.7554/eLife.71945.

New Undergraduate Engineering Science Program Approved

Technology is central to our society. Universities play a key role as innovation hubs in new technology development, by linking knowledge creation, workforce development and commerce. After a multi-year planning process with Brandeis stakeholders and Engineering education experts, the Brandeis Faculty and Board of Trustees has approved the creation of a distinctively Brandeisian undergraduate Engineering Science program, designed for ABET accreditation. Unlike other models in which Engineers are siloed in their own department or school, this interdepartmental program is designed to  maximize horizontal integration across and beyond the Sciences.  All hands are now on deck to make this program a reality.  Institutional Advancement is working closely with faculty to raise the funds necessary to meet our ambitious goals.

Science Engineering LogoTo build up this program, we will  capitalize on the existing synergy between the life and physical sciences, while enhancing core research areas with an emphasis on translating basic research to technological applications.  Our goal is to integrate the engineering curriculum with the social justice mission that is integral to Brandeis. We envision providing opportunities for our students and faculty to deeply engage in science, design, and problem-solving while participating in a curriculum and culture that grapples with issues of social justice, business ethics and sustainability. The curriculum will be designed with these aspirations by engaging faculty from all of arts and sciences, IBS and Heller.  Ultimately, we hope that this new program will give our students the tools to intervene in the world and challenge them to build a better one.

We welcome input from our friends and alums as we begin to engage in the task of building up this exciting new program.

First Rosbash-Abovich Award Recipients Announced

Michael Rosbash, the Peter Gruber Endowed Chair in Neuroscience and Professor of Biology and his wife, Nadja Abovich, established the Rosbash-Abovich Award as a way to inspire and acknowledge excellence in research by post-doctoral fellows and graduate students in the Brandeis life sciences. The Rosbash-Abovich award will be awarded annually.

The award honors the most outstanding papers published the previous year that have been authored by a Brandeis postdoctoral fellow and a Brandeis PhD student. In addition to the honor being selected, each winner is presented with a monetary award.

Future winners will present their talks at upcoming Volen Scientific Retreats, but due to COVID restrictions, the 2020 winners will be presenting their talks during the Molecular Genetics Journal Club meetings.

Most outstanding paper by a post-doctoral fellow

Michael O'Donnell

Michael O’Donnell, PhD

The 2020 winner for the most outstanding post-doctoral paper is Michael O’Donnell for the publication titled “A neurotransmitter produced by gut bacteria modulates host sensory behavior“. O’Donnell, is a former postdoc in the Piali Sengupta Lab. Sengupta said

Mike is a remarkable scientist and mentor. He single-handedly and independently established a new research direction in my lab. He also served as an informal mentor to many graduate students and has continued to do so even after he left my lab. I greatly appreciated our long discussions and arguments, and he is very much missed.

Sengupta also noted that O’Donnell was chosen to receive this award

on the basis of the creativity and novelty of his work that was published in Nature. The committee was particularly interested in nominating a researcher who was a driving force behind the work and Mike certainly fulfilled this criteria.

O’Donnell is now an assistant professor at Yale and recently formed the O’Donnell lab. He presented his talk to the Molecular Genetics Journal Club on December 2, 2020. He spoke about his work on neuromodulators produced by different bacteria.

Most outstanding paper by a PhD student

James Haber & Gonen Memisoglu

Professor James Haber & Gonen Memisoglu, PhD

The recipient of the 2020 award for the most outstanding PhD student paper is Gonen Memisoglu for the publication “Mec1 ATR Autophosphorylation and Ddc2 ATRIP Phosphorylation Regulates DNA Damage Checkpoint Signaling.“ She was a PhD student in James Haber’s lab. She received her PhD in 2018 and is currently a postdoctoral fellow at the University of Chicago. She will be presenting her talk at the Molecular Genetics Journal Club on February 2, 2021.

When asked about his former PhD student, Haber said

I was delighted to learn that Gonen was the recipient of the Rosbash/Abovich award for the best publication by a graduate student last year; but I had to ask “which paper” because Gonen made two important discoveries last year about the way cells respond to DNA damage. Gonen helped develop a highly efficient way to edit the yeast genome and to create dozens of very precise mutations in the Mec1 gene that is the master regulator of the DNA damage response.  When there is a chromosome break, the Mec1 protein phosphorylates a number of proteins that creates a cascade of signaling to prevent cells from progressing through mitosis until damage is repaired. Gonen discovered that the extinction of the this signal depended on Mec1’s autophosphorylation of one specific target and that changing that specific amino acid to one that could not be phosphorylated was enough to cause cells to remain arrested. She also identified several alterations of the Ddc2 protein that associates with Mec1 that were also critical for its normal activation.

During her time in my lab Gonen was a super hard-working and exceptionally insightful grad student, but also incredibly generous with her time, helping others in the lab

Hunting Novel Viruses in a Lab Course

Last Fall the Biology department mounted a new course (BIOL 152B),  the Virus Hunter Lab. This course combines practical experience in the lab with computer based approaches in bioinformatics. Students in the class isolated a type of virus that infects bacteria called a bacteriophage. In the wet lab, they learned basic microbiology techniques for isolating the viruses and basic molecular biology techniques for extracting the DNA of the viral genomes. With the biological material in hand the class prepared next generation sequencing libraries. The students assembled and annotated the complete genome of two previously unknown bacteriophage using next generation sequencing data from the samples they prepared. To find out more about it you can read their paper. Grad students Meghan Harris (MCB), their TA, and Tereasa Ho (Biotechnology) along with the inaugural group of undergraduate students are all authors on a paper recently published in the journal Microbiology Resource Announcements (MRA).

Harris MT, Ho TC, Fruchtman H, Garin ME, Kubatin V, Lu T, Xue L, Marr MT. Complete Genome Sequences of Two Vibrio natriegens Bacteriophages. Microbiology Resource Announcements. 2020;9(45).

Electron microscope image of the novel bacteriophage (VH2), photo by Jesse Cochrane

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