Data Diving for Genomics Treasure

Laboratories around the world and here at Brandeis are generating a tsunami of deep-sequencing data from organisms large and small, past and present. These sequencing data range from genomes to segments of chromatin to RNA transcripts. To explore this “big data” ocean, one can navigate the portals of the National Computational Biotechnology Institute’s (NCBI’s) two signature repositories, the Sequencing Read Archive (SRA) and the Gene Expression Omnibus (GEO).  With the right bioinformatics tools, scientists can explore and discover freely-available data that can lead to new biological insights.

Nelson Lau’s lab in the Department of Biology at Brandeis has recently completed two such successful voyages of genomics data mining, with studies published in the Open Access journals of Nucleic Acids Research (NAR) and the Public Library of Science Genetics (PLoSGen).   Publication of both these two studies was supported by the Brandeis University LTS Open Access Fund for Scholarly Communications.

In this scientific journey, the Lau lab made use of important collaborations from across the globe. The NAR study employed openly shared genomics data from the United Kingdom (Casey Bergman lab) and Germany (Björn Brembs lab).  The PlosGen study employed contributions from Austria (Daniel Gerlach), Australia (Benjamin Kile’s lab), Nebraska (Mayumi Naramura’s lab), and next door neighors (Bonnie Berger’s lab at MIT).  This collaborative effort has been noted at Björn Bremb’s blog, who has been a vocal advocate for Open Access and Open Data Sharing to improve the speed and accessibility of communicating scientific research.

tidal fly banner

In the NAR study, postdoctoral fellow Reazur Rahman and the Lau team devised a program called TIDAL (Transposon Insertion and Depletion AnaLyzer) that scoured over 360 fly genome sequences publicly accessible in the SRA portal.  Their study discovered that transposons (jumping genetic parasites) formed different genome patterns in every fly strain.  Common fly strains with the same name but living in different laboratories turn out to have very different patterns of transposons. Simply noting “Canton-S” or “Oregon-R” strains are used may not be enough to fully characterize a strain.  The Lau lab hopes to utilize the TIDAL tool to study how expanding transposon patterns might alter genomes in aging fly brains.

animals

The piRNAs from these animals were compared in the PLoS Genetics story

In the PLoSGen study, visiting scientist Gung-wei Chirn and the Lau team developed a novel small RNA tracking program that discovered Piwi-interacting RNA loci expression patterns from many mammalian datasets extracted from the GEO portal.  Coupling these datasets with other small RNA datasets created in the Lau lab at Brandeis, the Lau group discovered a remarkable diversity of these RNA loci for each species. For example, the piRNA genomic loci made in humans were quite distinct from other primates like the macaque monkey and the marmoset.  However, a special set of these genomic loci have been conserved in their piRNA expression patterns, extending across humans, through primates, to rodents, and even to dogs, horses and pigs.

These conserved piRNA expression patterns span nearly 100 million years of evolution, which is quite a long time for these types of loci to be maintained for some likely important function in mammals.  To test this hypothesis that evolution preserved these piRNAs for their utility, the Lau lab analyzed two existing mouse mutations in these loci.  They showed that the mutations indeed affected the generation of the piRNAs, and these mice were less fertile because sperm count was reduced.  The future studies from the Lau lab will explore how infertility diseases may be linked to these specific piRNA loci.

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.

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

 

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.

4th Annual Sprout Grants – Call for applications

Bring your research and entrepreneurial ambitions to life!

The Brandeis University Virtual Incubator invites member of the Brandeis Community (undergrads, grad students, postdoctoral fellows, faculty, staff) to submit an application for a “Sprout Grant”. These grants are intended to stimulate entrepreneurship on campus and help researchers launch their ideas and inventions from Brandeis to the marketplace.

This spring we will be awarding $50,000 to be shared amongst the most promising proposals.

Come get your questions about the Sprout grant answered at one of our upcoming information sessions.

Info sessions:

Tuesday      February 18th    1pm – 2pm

Tuesday      February 25th    10am – 11am

Thursday     February 27th    11am – noon

Tuesday      March 4th          11am – noon

All information sessions will be held in the Shapiro science center 1st floor library, room 1-03 (the glass walled room near the elevators).

Deadlines: Preliminary applications are due on Friday, March 7th

Benefits of participation:

  • Teams that are selected to submit full applications will be given assistance in further developing their ideas into an effective business pitch.
  • Sprout grant winners will be connected with an experienced mentor, and given further assistance in getting their ideas to market by the Office of Technology Licensing.
  • Previous winners have come from many departments: Neuroscience, Biology, Biochemistry, Physics and Computer Science. Some of the funded technologies have resulted in patent applications and are moving towards commercial development. Read more about previous winners from your department here: Sprout winners 2011, Sprout winners 2012, Sprout winners 2013.

For more information go to our website (http://www.brandeis.edu/otl/grants/index.html) or contact Melissa Blackman at melblack@brandeis.edu.

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