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.

Taste and smell are intertwined in the rat brain

A recent paper in Current Biology titled “A Multisensory Network for Olfactory Processing” from the Katz Lab in Psychology tackles the question of where in rat brain the senses of taste and smell are processed, and just how distinct the two senses are. In addition to Katz, authors on the paper include former postdoctoral fellows Joost Maier and Jennifer Li, as well as Neuroscience graduate student Meredith Blankenship.

The paper discusses their finding that the tongue and the nose work together to help you decide what potential foods are actually good to eat. This intimate cooperation leads to an intertwining and interdependence of function; everyone who has had a cold knows that things don’t taste right when the sense of smell is blocked (by snot). They now show that the opposite is true as well–specifically, that the part of the cortex known to be responsible for taste is also required for the sense of smell.

Recordings from taste and olfactory cortex

First, they show that there is a strong neural connection between taste cortex (GC) and olfactory cortex (PC): this connection ensures that information about tastes in the mouth reaches the latter from the former, but also ensures that a constant chatter of action potentials (the language of the brain) flows between the two, even in the total absence of a substance on the tongue. Thus, switching those taste cortex neurons off both removes any evidence of taste information in olfactory cortex AND changes the way olfactory cortex deals with odor information arriving directly from the nose. The result of this impact is striking: a rat utterly fails to recognize a familiar odor when taste cortex is silent; the taste system is a part of the smell system.

The implications of this finding for neuroscience are far-reaching. It suggests a major breakdown of the basic dogma that the different sensory systems, each of which originate in distinct sense organs (the nose for smell, the tongue for taste) process their input independently. In fact, the brain likely doesn’t “see” tastes and smells as separate at all, but as unified parts of holistic objects…FOOD.

Maier JX, Blankenship ML, Li JX, Katz DB. A Multisensory Network for Olfactory Processing. Curr Biol. 2015.

TIDAL-Fly: a new database resource of Transposon Landscapes for understanding animal genome dynamics.

We tend to think of our genomes as nicely-ordered encyclopedias,  curated with only useful information that makes up our genes.  In actuality, nature and evolution is extremely sloppy.  All animal genomes, from us humans to the simple fruit fly, are littered with genetic baggage.  This baggage is sizeable, making up at least 11% of the fly genome and more than 45% of our genome.  The scientific term for this baggage is transposable elements (TEs) or transposons, which are mobile entities that must copy themselves to other places of the genome to ensure their survival during animal evolution.

Because there are so many copies of transposons, they can be difficult to analyze by most standard genetic methods. Brandeis postdoctoral fellow Reazur Rahman and a team in Nelson Lau’s lab have formulated a new tool called the Transposon Insertion and Depletion AnaLyzer (TIDAL). TIDAL aims to provide an accurate and user-friendly program to reveal how frequently transposons can move around in animal genomes.  Currently, the TIDAL tool has been applied to over 360 fruit fly genomes that have been sequenced and deposited in the NIH NCBI Sequencing Read Archive.  The outputs from this program are available to the whole genetics community through the TIDAL-FLY database.

tidal fly banner

The TIDAL-Fly database will allow geneticists to pick their favorite fly strain and see if a transposon has landed near to their gene and perhaps affect gene expression. Fruit flies are key model organisms utilized by many researchers, including here at Brandeis, to study human diseases, from infertility to insulin signaling to aging to sleep disorders.  Since these new transposon insertions are not available in the standard genome databases, this tool and website may provide answers to previously puzzling genetic effects not revealed by typical DNA sequencing studies.  It is Reazur’s and the Lau lab’s goal to continue updating the TIDAL-Fly database with more genomes as fly genome re-sequencing becomes easier and easier to perform.

see also: Rahman R, Chirn GW, Kanodia A, Sytnikova YA, Brembs B, Bergman CM, Lau NC. Unique transposon landscapes are pervasive across Drosophila melanogaster genomes. Nucleic Acids Res. 2015.

Putting “umpolung” to work in synthesis of nitrogen-bearing stereocenters

Professor Li Deng‘s lab in the Brandeis Chemistry Department has recently published a high-profile paper in Nature, disclosing an important advance in the chemical synthesis of organic molecules containing nitrogen. Li Deng writeup 1

A great number of important drugs contain at least one nitrogen atom connected to a “stereogenic” carbon atom. Stereogenic carbons are connected to four different groups, making possible two different configurations called “R-” or “S-”. In synthesizing a drug, it can be disastrous if the product does not have the correct R/S configuration.  For instance, the morning-sickness drug Thalidomide caused birth defects in ~10,000 children because it was a mixture of R and S molecules.Li Deng writeup 2

Selective preparation of only R or only S molecules containing nitrogen is a major challenge in organic chemistry. Many recent approaches have formed such stereocenters by use of an electron rich “nucleophile” to attack an electron poor “imine”. Deng is now the first to report an unconventional strategy in which the polarity of the reaction partners is reversed. In the presence of base and a creatively designed catalyst, the imine is converted into an electron rich nucleophile, and can attack a variety of electrophiles. Deng’s catalysts are effective in minute quantities (as low as 0.01 % of the reaction mixture), and yield products with R- or S- purities of 95-98 %.

In addition to Professor Deng, authors on the paper included former graduate student Yongwei Wu PhD ’14, current Chemistry PhD student Zhe Li, and Chemistry postdoctoral associate Lin Hu.

Wu Y, Hu L, Li Z, Deng L. Catalytic asymmetric umpolung reactions of imines. Nature. 2015;523(7561):445-50. (commentary)

Summer 2015: “Introduction to Microfluidics Technology”

Students are in the cleanroom during training.

Students in the clean room during training

The annual one-week course offered during the summer of 2015 is “Introduction to Microfluidics Technology” (June 22 – 26). It will be held at Brandeis University and sponsored by the National Science Foundation’s Bioinspired Soft Materials Research Science and Engineering Center (MRSEC) at Brandeis. It is intended for graduate students, post docs, faculty and industrial scientists and engineers interested in utilizing microfluidic technology in their work, in both physical sciences and life sciences, and does not assume any specific prerequisites.

SUMMER COURSE ANNOUNCEMENT 2015

Microfluidic Xmas Tree

“Scientist of small things”

IMAGE: BMXIMAGE (from Forbes India)

IMAGE: BMXIMAGE (from Forbes India)

Forbes India recently named Brandeis post-doc alumna Prerna Sharma as one of India’s “30 under 30”. Sharma, who worked in Prof. Zvonimir Dogic’s group in Physics, is currently an Assistant Professor at the Indian Institute of Science (IISc), Bangalore.

Read the original at Prerna Sharma: The scientist of small things, or perhaps her 2014 Nature paper on Hierarchical organization of chiral rafts in colloidal membranes

 

Deep inside a worm’s nose

In a new paper in eLIFE, a team spearheaded by Brandeis postdocs David Doroquez and Cristina Berciu provide a strikingly detailed look at key structures called cilia on neurons involved in sensory perception in the nematode C. elegans. Primary cilia are the antenna-like structures onsensory neurons that gather information about the animal’s environment, such as chemicals, temperature, humidity, and touch. The genetic tools available to manipulate individual, identifiable neurons in C. elegans make worms an excellent model organism to study the assembly and function of cilia. This study requires a description of the structure of the cilia and their immediate surrounding glial support cells, and this new paper, a collaboration of the Sengupta and Nicastro labs, provides high-resolution 3D models showing how diverse and specialized these structures are.

worm-01-2

A bouquet of sensory antennae. The 3D ultrastructure of all sensory cilia
and other neuronal projections in the head of the soil roundworm C.
elegans have been reconstructed using serial section transmission electron
microscopy. Shown are 3D isosurface-rendering models emerging from a
transmission electron microscopic cross-section of the worm.

The key techniques in this study were serial section transmission electron microscopy and electron tomography, with structures well-preserved by high-pressure freezing and freeze-substitution. With these techniques, the authors achieved the first high-resolution 3D reconstructions of 50/60 cilia from C. elegans. They describe several previously uncharacterized features — for example, there are distinct types of branching patterns – in one, the two cilia originate from independent basal bodies (as previously seen in Chlamydomonas). In the second, the cilia branch after the basal transition zone, the ciliary gatekeeper region. In the latter case, this basically means that whatever is needed for the cilia to branch has to be transported through the transition zone, suggest there might be novel mechanisms of ciliary protein trafficking. In a third pattern, the branching occurs proximally before the transition zone, and represent therefore dendritic microvilli, rather than ciliary branching. The study also showed different organizations  of microtubules in different cilia types and vesicles in regions of the cilia which have never been seen before, again pointing to new mechanisms of protein transport. They also describe new cilia-glial interactions, which might suggest that cilia and glia talk to each other.

For more about these structures (with lots of pretty pictures and movies), see:

Fast-spiking interneurons and the critical period

How do children learn to play instruments and speak languages so much easier than adults, and why does brain damage result in worse outcomes in the mature brain vs. the young brain?  These questions are central to the study of how “critical periods” are regulated in the brain.

fs-interneuron

Electron micrograph from a single 70 nm cross-section through a fast-spiking parvalbumin-containing (gold labeling = white dots) presynaptic terminal forming a synapse (red dots) with a pyramidal soma. Original colors are inverted, contours have been raised and membranous structures are highlighted in aqua for ease of visualization. Presynaptic vesicles (colored ovals) within perisomatic fast spiking terminals mostly cluster within ∼200 nm of the synapse, with a few close enough (≤2 nm) to be deemed docked.

Critical periods in brain development define temporal windows when neuronal physiology and anatomy are most sensitive to changes in sensory input or experience (e.g. sound, touch, light, etc.).  The maturation of inhibitory cells that release the neurotransmitter GABA, especially a subset called fast-spiking (FS) interneurons, is thought to gate this period of neuronal ‘plasticity’ in the mammalian primary visual cortex.  However, it has remained unclear what aspects of FS cell development are important for permitting this period of neuronal malleability in the visual cortex. A new paper in Journal of Neuroscience from the Turrigiano lab addresses the question.

To explore how FS cell development might be linked to critical period plasticity, Brandeis postdoc Marc Nahmani and Professor Gina Turrigiano employed a well-established assay for cortical plasticity in visual cortex called monocular deprivation (MD), and measured FS cell connections using confocal and electron microscopy, as well as optogenetic stimulation of the FS cell population (i.e. shining light onto FS cells possessing light-gated channels to make them fire action potentials).

Following up on previous work from the Turrigiano lab (Maffei et al., 2006), they found that MD induces a coordinated increase in FS interneuron to pyramidal cell (the major excitatory output cells of the cortex) pre- and postsynaptic strength.  These changes occur if MD is performed during, but not before the critical period in visual cortex, suggesting they may play a role in gating this period of heightened neuronal plasticity.  Future studies are aimed at determining the timeline for these changes across the extent of the critical period in visual cortex.

see: Nahmani M, Turrigiano GG (2014) Deprivation-Induced Strengthening of Presynaptic and Postsynaptic Inhibitory Transmission in Layer 4 of Visual Cortex during the Critical Period. Journal of Neuroscience 34:2571-2582.

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