How regulatory sequences evolve in fruit flies

An IMP-Brandeis collaboration reveals the evolution of regulatory sequences in Drosophilids

By Yuliya Sytnikova and Nelson Lau

Enhancers are cis-regulatory DNA sequences that influence the promoters of genes, but identifying enhancers is not a straightforward process. Previously, the Stark lab developed a method for genome-wide enhancer detection called STARR-seq, (Arnold, Gerlach et al. 2013), that allowed them to identify thousands of enhancer sequences around the Drosophila melanogaster genome. In the most recent issue of Nature Genetics, a collaboration between the Stark lab of the IMP (Institute of Molecular Pathology) in Vienna, Austria, and the Lau lab at Brandeis University examines this hypothesis by studying the conservation of enhancer regulatory regions during Drosophilid fly evolution.

To ask if enhancers from D. melanogaster enhancers are also conserved in other Drosophila species in their sequences and locations, the Stark lab extended the STARR-Seq approach to D.yakuba and D.ananassae, which are separated from D.melanogaster by 11 and 40 million years ago, respectively (Arnold, Gerlach et al. 2014). Interestingly, this study also revealed hundreds of new sequences that gained enhancer function differentially between D.yakuba, D.ananassae, and D.melanogaster.

However, to test if these new sequences meaningfully direct different gene expression changes, the Lau lab conducted a targeted mRNA profiling experiment in purified endogenous follicle cells from D.yakuba and D.ananassae. The Stark lab had initiated the STARR-Seq analysis in an Ovarian Somatic Cell (OSC) line, which originated from the follicle cells of D.melanogaster, therefore the profiling of endogenous follicle cells from D.yakuba and D.ananassae was critical. The Lau lab achieved this using a methodology they developed for profiling Piwi-interacting RNAs from these cells (Matts, Synikova et al. 2013).

Figure 6: Evolution of enhancer activity in OSCs and gene expression in follicle cells in vivo.

nature_genetic_fig6

Arnold CD, Gerlach D, Spies D, Matts JA, Sytnikova YA, Pagani M, Lau NC, Stark A. Nat Genet. 2014 Jun 8. doi: 10.1038/ng.3009. [Epub ahead of print] Quantitative genome-wide enhancer activity maps for five Drosophila species show functional enhancer conservation and turnover during cis-regulatory evolution.

Matts JA, Sytnikova Y, Chirn GW, Igloi GL, Lau NC. Methods Mol Biol. 2014;1093:123-36. doi: 10.1007/978-1-62703-694-8_10. Small RNA library construction from minute biological samples.

 

“Age, Hearing, and Speech Comprehension”: A Festschrift for Art Wingfield

artWingfieldBlogA one-day event will be held on July 22, 2014 at the Shapiro Campus Center Theater to honor Art Wingfield, the Nancy Lurie Marks Professor of Neuroscience, for his 40+ years of research and teaching at Brandeis. During his time at Brandeis, Art has made contributions to the areas of speech comprehension, cognitive aging, memory, and aphasia and has mentored numerous PhD students, research assistants and postdocs. Art has inspired countless other students in his course on Human Neuropsychology.

Some of the speakers will include former lab members and prominent researchers in the field:

  • Mark Eckert, Department of Otolaryngology,
    Medical University of South Carolina
  • Murray Grossman, Department of Neurology,
    University of Pennsylvania
  • Stefanie Kuchinsky, Center for Advanced Study of Language,
    University of Maryland
  • Jonathan Peelle, Department of Otolaryngology, Washington University in St. Louis
  • Kathy Pichora-Fuller, Department of Psychology, University of Toronto Mississauga
  • Robert Remez , Department of Psychology, Columbia University
  • Bruce Schneider, Department of Psychology, University of Toronto Mississauga
  • Liz Stine-Morrow, Department of Educational Psychology and Beckman Institute, University of Illinois, Urbana-Champaign

For more information about this event can be found at www.artwingfieldfest.com/.

If you are interested in attending, please register at by July 5th.

Brandeis IGERT Summer Institute June 16 – June 26, 2014

The second Brandeis IGERT Summer Institute begins this Monday, June 16th in Goldsmith 300 and runs through Thursday, June 26th. This will consist of a variety of talks by faculty and students on subjects in the mathematical sciences. While this is part of the IGERT training program, aimed at graduate students working across the spectrum of the mathematical sciences, we invite the Brandeis community to attend any of the talks that catch their eye. Speakers include:

  • Chris Santangelo (U Mass Amherst)– “Shape and mechanics of origami folding”
  • Matthew Headrick — “Introduction of quantum information theory”
  • Bulbul Chakraborty and Blake Lebaron — “Applications of Statistical Mechanics to Finance”
  • Daniel Ruberman — “Introduction to Knot Theory”
  • Paul Miller — “Feedback control in neural firing”
  • Albion Lawrence — “An introduction to inflation and gravity waves”
  • Eli Putzig — TBA
  • Honi Sanders — TBA
  • Tony Ng — TBA

and a schedule can be found at http://www.brandeis.edu/igert/calendar/index.html  or in the Brandeis Science Seminars listings.

We will be having lunch in the Volen bridge; please bring your own and join us!

Why we love basic research

Brandeis PhD students Jonathan Napoline (Graduate Program in Chemistry, Thomas lab) and Sara Haddad (Graduate Program in Neuroscience, Marder lab) tell PBS NewsHour why they’re excited about basic research

 

 

Michael Kosowsky ’14 receives NSF Graduate Research Fellowship

KosowskyMichael Kosowsky ’14, who majored in both physics and mathematics at Brandeis, has been awarded a National Science Foundation Graduate Research Fellowship in astronomy and astrophysics.  The fellowships, which are awarded based on a national competition, provide three full years of support for Ph.D. research and are highly valued by students and institutions. Kosowsky worked with Prof. David Roberts in the Physics Department on analyzing the polarization of the X-ray binary SS 433 with the purpose of figuring out the magnetic field structure of the source.  He will be pursuing a Ph.D. in physics at Harvard University starting this fall.

Other 2014 NSF Fellowship recipients from Brandeis include:

Alex Dainis  (BS ’11, Biology, Film, Television, Interactive Media), Stanford University
Abby Finkelstein (BS ’13, Neuroscience),  Arizona State University
Lamia Harper (BS ’12, Biology), NYU
Ariel Hyre  (BS ’13,  Chemistry), Boston University
Anatoly Rinberg (BS ’11, Physics, Mathematics), Stanford University
Seth Werfel  (BA ’10, Economics), Stanford University

 

Brandeis Posse at the White House

President Fred Lawrence and Chemistry Professor Irving Epstein visited the White House on March 31 to discuss the Brandeis Science Posse at an event celebrating the expansion of the program to a total of 10 institutions across the country.  Attendees included Presidential Science Advisor John Holdren and other representatives of the executive branch, presidents of the STEM Posse schools, and current and former members of the Brandeis Science Posse.  The program began at Brandeis in 2008 under Epstein’s direction with a grant from the Howard Hughes Medical Institute.

white house 3-31-14

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:

Professors Seth Fraden and Irv Epstein interviewed on NPR

Professor Seth Fraden (Physics) and Professor Irv Epstein (Chemistry) were interviewed on Radio Boston, WBUR  about their research confirming Alan Turing’s Morphogenesis Theory.

Here’s the story:

http://radioboston.wbur.org/2014/03/27/brandeis-turing-morphogenesis

Here’s how to listen:

http://radioboston.wbur.org/listen

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