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Natasha Baas-Thomas & Don Katz Receive 2022 Gilliam Fellowship

August 17, 2022 By

Natasha Baas-Thomas and her thesis adviser, Donald Katz, Professor of Neuroscience have received the 2022 HHMI Gilliam Fellowship. The Gilliam Fellowship is awarded to both the graduate student and the student’s adviser with each pair receiving an annual award of $53,000 for up to three years.

The Gilliam Program goal is to assist graduate students from populations historically excluded and underrepresented in science. Recipients are chosen based upon their scientific and leadership potential, the quality of and commitment to mentorship and to the development of a more inclusive environment in the sciences.

Natasha noted “I am honored to be selected as a 2022 Gilliam Fellow. I hope to use the award to advance my leadership abilities as I work towards a professorship position. I am also excited by the mentorship focus of this award, which I can implement to improve diversity and inclusivity at Brandeis.”

Donald Katz said “I’m thrilled that the HHMI has recognized Natasha to be both a stellar scientist and a vital force for change in the field — a future leader. And I’m excited to learn from the expert mentorship training team that HHMI has put together. The Gilliam program is quite unlike anything that has come before, in the multi-pronged approach that it takes to promoting diversity and opportunity in science.”

When discussing her research plans, Natasha said “during my PhD in the Katz lab, I will be studying the gustatory system in rats. Specifically, I will be investigating the signal sent from the gustatory cortex to the motor circuit. Focusing on how the gustatory cortex guides the decision to either consume or expel a taste stimulus.”

 

Filed Under: awards, division of science, division of science, labs, Neuroscience Tagged With: , , , ,

BUPA opens applications for Invited Postdoc Research Colloquium

August 8, 2022 By

IPRC 2022 Speaker

The Brandeis University Postdoctoral Association (BUPA) is organizing its yearly Invited Postdoc Research Colloquium (IPRC) for the academic year 2022-2023. BUPA is inviting two senior neuroscience postdocs to Brandeis to present their research and visit the Brandeis community. Selected speakers will give an hour-long seminar, meet with faculty one-on-one, and engage in informal discussion with Brandeis postdocs over lunch and dinner. This provides a great opportunity for the speakers to receive scientific feedback and increase their visibility in the scientific community, two essential aspects for their future job search. Also, of course, this is an equally great opportunity for the Brandeis community to engage in fruitful scientific discussion and learn about exciting research performed outside of the Brandeis campus.

Interested postdocs should send an updated CV as well as an abstract of their research (maximum 250 words) to BUPA (bupa@brandeis.edu). Seminars will be organized in person and funds for travel, accommodation and food will be provided for the speakers. Virtual presentations will be organized should the need arise. Women and underrepresented minorities are strongly encouraged to apply. The application deadline is August 31, 2022.

For additional information, please contact BUPA at bupa@brandeis.edu.

Filed Under: division of science, division of science, division of science, General, labs, Neuroscience, postdocs Tagged With: , ,

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

May 5, 2022 By

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.

Filed Under: Biology, division of science, division of science, division of science, General, grad students, labs, Neuroscience Tagged With: , , , , , ,

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

April 25, 2022 By

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.

Filed Under: Biology, division of science, division of science, division of science, General, grad students, labs Tagged With: , , , , ,

Schmidt-Rohr examines why plants need two different photosystems

December 15, 2021 By

In a recent paper in Life (Basel), Klaus Schmidt-Rohr, Professor of Chemistry, introduces a self-explanatory description of the energetics of photosynthesis in plants, the so-called EZ-scheme. It shows the energies of molecules in kJ/mol instead of the classical Z-scheme’s shifted energy differences that are misleadingly encrypted in volts. Unlike its predecessor, the EZ-scheme includes the Kok cycle in the water-splitting complex, charge separation after photon absorption, and the Calvin cycle with carbohydrate synthesis (in a simplified form). It also shows O2 correctly as a high-energy product, due to its relatively weak double bond, and demonstrates that Photosystem II pumps more of the absorbed photon energy into O2 than into the plant.

This paper provides the first valid explanation of why plants need two different photosystems: PSII mostly extracts hydrogen (as protons plus electrons) from H2O, producing PQH2 (plastoquinol), and generates the energetically expensive product O2, providing little energy directly to the plant. PSI is needed to produce significant chemical energy for the organism, in the form of ATP, and to generate a less reluctant hydrogen donor, NADPH. This work fundamentally revises received notions of the energetics of photosynthesis, by pointing out the classical Z-scheme’s bewildering implication that H2O gives off electrons spontaneously to chlorophyll while releasing energy, and by showing that the concept of energy transport by “high-energy electrons” in photosynthesis is misguided, since energy and electrons flow in opposite directions.

Figure #1 from Schmidt-Rohr paper

Figure 1 Simplified EZ-scheme of the energetics of photosynthesis in plants, converting H2O and CO2 to O2 and carbohydrate, [CH2O]. The direction of energy transfer and release is indicated by straight red arrows at the top, formal hydrogen transfer by blue dashed curved arrows at the bottom of the diagram. Three dots … indicate omitted redox reactions.

Schmidt-Rohr K. O2 and Other High-Energy Molecules in Photosynthesis: Why Plants Need Two Photosystems. Life (Basel). 2021 Nov 5;11(11):1191.

Filed Under: chemistry, division of science, labs Tagged With: , ,

Han paper describes electrochemical switching of arylazopyrazole & heat release

December 8, 2021 By

Research image from paperMihael Gerkman and Prof. Grace Han in the Department of Chemistry report the first demonstration of redox-induced energy release from molecular solar thermal (MOST) compounds in condensed phases, in collaboration with a team of Prof. Matthew Fuchter at Imperial College London. MOST compounds that utilize light-induced chemical isomerization for harnessing solar photon energy have emerged as an alternative to photovoltaics and artificial photosynthesis, enabling a closed-system solar photon energy storage and controlled release. Despite the discovery of various photoswitch systems that show improved photon energy storage efficiencies, the efficient and complete energy release from such photoswitches has remained a major challenge.

This work describes electrochemically-induced switching of arylazopyrazole-based photoswitches. The switching itself is electrocatalytic, requiring only a substoichiometric amount of charge, and its efficiency is improved by over an order of magnitude in the condensed phase compared to in solution. Moreover, electrochemically-induced switching affords a significantly higher completeness of switching than what could be achieved photochemically, which addresses the critical limitation of various azoheteroarene-based MOST materials. We envision that this work will promote exploration of the use of an electrical trigger for MOST material applications for a wide variety of photoswitches.

Jake L. Greenfield‡, Mihael A. Gerkman‡, Rosina S. L. Gibson, Grace G. D. Han*, and Matthew J. Fuchter* J. Am. Chem. Soc. 2021, 143, 37, 15250–15257. (‡ equal contributions) Publication Date: September 14, 2021.

Filed Under: chemistry, division of science, labs Tagged With: , ,

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