Turrigiano lab uncovers sources of neuronal heterogeneity

High activity neurons have greater instrinsic excitability and response to local inputs, but no difference in total input type or amount

Mammalian cortex has long been one of the most widely studied systems in neuroscience, dating back to the pioneering work of Santiago Ramon y Cajal in the late 19th century. The cortex is much larger in primates than other mammals, and is thought to be responsible for the advanced cognitive abilities of humans. Today, models of cortical connections and computations form the basis for some of the most powerful deep learning paradigms. However, despite this success, there is still much that is unknown about how cortex functions. One feature of cortex that has recently been discovered is that neurons that appear to be similar to each other can have very different baseline activity levels: some neurons are 100x more active than their neighbors. We don’t know how neurons that are otherwise highly similar in shape and genetic makeup can maintain such different activity levels, or if the neurons with high and low activity levels have different functions in the brain. These neurons are otherwise so similar to each other that it is difficult to tell them apart without recording their activity directly, and current techniques for recording the activity of many neurons simultaneously in live animals do not allow us to later re-identify them for further study.

In a paper recently published in Neuron, the Turrigiano lab, led by postdoctoral researcher Nick Trojanowski, reported a new approach for permanently labeling high and low activity neurons in live animals, and then determining what makes them different. To do this they used a fluorescent protein called CaMPARI2 that changes from green to red as activity increases, but only when exposed to UV light. By shining UV light into the brain, they caused neurons with high activity to turn red, while neurons with low activity remained green. This procedure allowed them to run a series of tests on high and low activity neurons to identify differences between them. They found that high activity neurons would intrinsically generate more activity than low activity neurons when presented with the same stimulus. These high activity neurons also receive more excitatory input specifically from nearby neurons of the same type. Surprisingly, however, they found that the total amount of excitatory and inhibitory input that high and low activity neurons received from other neurons was not a major factor in determining their activity levels. Together, these results tell us that the differences in activity between neurons are due to intrinsic differences, as well as their pattern of connectivity to their nearby partners. This has deep implications for how the networks that underlie cortical computations are built and maintained.

With these tools in hand, it is now possible to further explore the differences between high and low activity neurons. Do these neurons serve different functions? Are the baseline activity levels specified from birth? How do these activity levels affect the mechanisms of plasticity that are responsible for learning and memory? The recently published results represent just the tip of the iceberg of information that can be learned with this new technique, in the mammalian cortex as well as other brain regions.

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

Alum, Past Postdoc Receive Awards from Breakthrough Prize Foundation

Netta Engelhardt

Netta Engelhardt. photo: MIT

Lisa Piccirillo

Lisa Piccirillo. photo: Quanta Magazine.

Lisa Piccirillo, a recent Brandeis postdoc and Netta Engelhardt, a Brandeis undergraduate alumni have received two awards from the Breakthrough Prize Foundation. While the Breakthrough Prizes are intended to help scientific leaders gain financial freedom, the New Horizons award and the Maryam Mirzakhani New Frontiers Prize focus on young scientists early in their careers.

The Maryam Mirzakhani New Frontiers Prize is awarded to early-career women mathematicians. Lisa Piccirillo received this prize for her work in resolving the Conway Knot problem. Piccirillo was a postdoc working with Daniel Ruberman, Professor of Mathematics, from 2019 until her recent appointment as Assistant Professor at Massachusetts Institute of Technology.

Netta Engelhardt, is part of a group that received the 2021 New Horizons in Physics Prize. Netta and three other scientists were awarded for their research in calculating the quantum information content of a black hole and its radiation. Engelhardt is currently an Assistant Professor of Physics at Massachusetts Institute of Technology. She was a 2011 graduate who majored in Physics. She received a NSF Graduate Research Fellowship prior to graduating from Brandeis.

 

Pump without pumps

By Kun-Ta Wu, Ph.D.

Pumping water through a pipe solves the need to provide water in every house. By turning on faucets, we retrieve water at home without needing to carry it from a reservoir with buckets. However, driving water through a pipe requires external pressure; such pressure increases linearly with pipe length. Longer pipes need to be more rigid for sustaining proportionally-increased pressure, preventing pipes from exploding. Hence, transporting fluids through pipes has been a challenging problem for physics as well as engineering communities.

To overcome such a problem, Postdoctoral Associate Kun-Ta Wu and colleagues from the Dogic and Fraden labs, and Brandeis MRSEC doped water with 0.1% v/v active matter. The active matter mainly consisted of kinesin-driven microtubules. These microtubules were extracted from cow brain tissues. In cells, microtubules play an important role in cell activity, such as cell division and nutrient transport. The activity originates from kinesin molecular motors walking along microtubules. In cargo transport, microtubules are like rail tracks; kinesin motors are like trains. When these tracks and trains are doped in water, their motion drives surrounding fluids, generating vortices. The vortices only circulate locally; there is no global net flow.

Wu-Pump without Pumps

Figure: Increasing the height of the annulus induces a transition from locally turbulent to globally coherent flows of a confined active isotropic fluid. The left and right half-plane of each annulus illustrate the instantaneous and time-averaged flow and vorticity map of the self-organized flows. The transition to coherent flows is an intrinsically 3D phenomenon that is controlled by the aspect ratio of the channel cross section and vanishes for channels that are either too shallow or too thin. Adapted from Wu et al. Science 355, eaal1979 (2017).

[Read more…]

From PhD to Life

By Craig W. Stropkay, (PhD ’13, Molecular and Cell Biology, Ren lab)

Reach for the stars, they said. You should definitely go get your PhD, you’d be great for it, they said. Well, I guess they did have a point. Pursuing my doctorate degree in Molecular Biology at Brandeis was definitely one of the most challenging things that I have ever had to do in my life. I could spend hours telling you about the long hours I spent trying to construct my dissertation or the countless nights that I had to wake up and drive into the lab from Medford just to “feed” my cells — but that’s not the point of this article. I want to talk about something that I wish was more openly discussed when I first started my journey towards pursuing a PhD. Something that I believe is important to anyone who is currently working their way towards earning their doctoral degree: a job.

Now I know what you may be thinking: why would I need to worry about a job when I know I will continue onto a postdoc and then a tenure-track academic post? Isn’t that what everyone does? That is precisely my point. Don’t get me wrong: there is absolutely nothing wrong with continuing a career in academia upon completion of your doctorate. It takes a lot of patience, skill, and dedication to remain in the field after you have literally spent years becoming an expert in everything dealing with Life Science. Maybe you’ve considered going that route, feeling that your choices are limited. Many people believe that apart from academia, their only “alternative” option is to go into industry and work in biotech or pharma.

Image from Naturejobs article

[Read more…]

Introduction to Microfluidics Technology – June 13-17, 2016

2016 MRSEC Summer Course Announcement

Registration for our annual, one-week summer course, “Introduction to Microfluidics Technology” at Brandeis University, near Boston, MA, is now open. The application deadline is March 31, 2016.

Introduction to Microfluidics Technology is a hands-on laboratory course sponsored by the National Science Foundation’s Bioinspired Soft Materials Research Science and Engineering Center (MRSEC) at Brandeis. It will be offered during the week of June 13 ‐ 17, 2016. The course is intended for graduate students, post docs, faculty, and industrial scientists/engineers interested in utilizing microfluidic technology in their work, both in the physical and life sciences. The course does not assume any specific prerequisites.

“Introduction to Microfluidics Technology” (June 13 – 17, 2016)
will be taught by Dr. Nathan Tompkins.

The $750 fee covers course tuition, housing in double-occupancy rooms, and breakfast/lunch/coffee from Monday through Friday. Single rooms are not available. Local students who do not need housing will pay a non-resident fee of $500 (cash and check only please).

More information is available.

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