Behind the cover

Getting a cover image for a journal was a first for me. As such I thought it would be interesting to revisit the behind the scenes. I am going for a short recap.

Initially when the paper was accepted the editor encouraged us to sugget a cover image. We (actually the Broad people, Manfred, Brian, and Aviv) recruited Sigrid Knemeyer who collected ideas and came up with some concept images. We (the three mentioned above, Moran, and me) then had several rounds of emails with Sigrid where each of us made comments, said what we liked or not about the options. Sigrid came up with a more detailed concept, which we sent to the editor. The editor wasn't too excited about it, and so we went back to the drawing board.

This time Sigrid, came up with four initial concepts.

We really liked some elements of each, but thought that the vortex of letters does not capture the idea of short reads. The stacks and stacks of papers was also nice, but didn't make it clear that the reads are short.

The next concept was to replace stacks of papers with short strips, like fortunes (as in fortune cookies), and combine it with the vortex.

We really liked this, but the final touch was adding the assembled sequence coming out of the vortex. This and change of color tone resulted in the concept that we sent to the journal.

They really liked it, and sent it to their graphic editors who came up with the final version. 

As you can see, they dispensed with the fortune-cookie strips, but kept the letters in "words" that capture the idea of short fragments and made other visual changes.

In conclusion, this was an interesting process. Sigrid was great in making this happen, and deserve a lot of credit. Thanks!

We made the cover!

Our paper on transcript assembly appeared online few weeks ago. Now the actual issue came out, and we made the cover, with a striking image.

The idea came out of iterations between all of us (Manfred Grabher, Brian Haas, Moran, Aviv and me) and  Sigrid Knemeyer who is an artist/illustrator working at the Broad Institute. Sigrid was great in developing the concept with our input of rough concepts, and this whirlwind was the final outcome.

Party: One Farewell + Two Welcome

Recently it seems that we have many farewell party. Another one today, to celebrate Noa's graduation and to say farewell on her departure to the Weizmann Institute. At the same time we also welcomed two new additions to the extended lab family: Oren and Daniela who born recently.

We had a nice picnic in a park near Jerusalem, and enjoyed the presence of current and recent lab members and the many young children of the next generation. As noted by few participants, the lab has been extremely productive on that front...

Substantial Histone Reduction Modulates Genome-wide Nucleosomal Occupancy and Global Transcriptional Output

The recent wave of publications seem to continue, and another paper just appeared in PLoS Biology. Like the previous one, this one was in the reviewing rounds for very long, and so we are very happy that it finally appeared.

This project is a collaboration with the group of Alessandra Agresti and Marco Bianchi from San Raffaele University in Milan. They are part of a European consortium that we are also members of, and they approached us to get help on dealing with nucleosome organization. Assaf got involved, into what was dubbed "The Italian Job" in lab meeting. After almost two years, the result is an impressive article.

To summarize the basic idea, the experiments by Barbara Celona, the main author, and other member's of the Milan group show that deletion in a key gene reduces the number of nucleosomes in the genome. As a result the DNA strands are packed by smaller number of nucleosomes. By mapping the locations of these nucleosomes we can see if nucleosome reduction leads to uniform change in density, or preferential reduction at particular locations, and what is the effect on transcription.

Source: PLoS Biology Synopsis by Robin Mejia

Our results show that nucleosome loss is mostly in locations that are less packed in normal cells, and moreover, that this loss correlates with increased transcription.

Cool!

Presidential Conference

This week we participated in the Israeli President's annual conference. This is a the place where important people from Israel and abroad come to talk about the future of the country, the region, and the world.

The Hebrew University was a co-sponsor of the event, and had its own space to presents research highlight. The target audience was not scientifically minded, so the message was to be kept at high level. Each participating lab had a small space where a large poster was presented on a table. We had TV monitors showing a movie about our lab.

Assaf and Avital participated as guides, and got to see the important people and even to talk with few. We did manage to get to hear some of the sessions, although I suspect the main action at these events in beyond the scenes.

The Comeback + Visitors

About three months ago Moran went off on a maternity leave. Today was the official first step on returning to academic work. To make the transition easier she was accompanied by her family. We got a chance to meet the family and the joy young ones bring.

Another weekend diving

Two weekend days to enjoy diving in Eilat. Many good sights and nice company of local people and fellow divers.

Patterns and Mechanisms of Ancestral Histone Protein Inheritance in Budding Yeast

Hot from the (virtual) press! A paper that we have been working on for almost a year appeared today in PLoS Biology. This is three way collaboration between Fred van Leeuwen's group at the Netherlands Cancer Institute, Ollie Rando's group at UMass Medical School and our group. The work on our end was mostly Assaf's who is a co-first author. 

The interesting aspect of this paper is that using a trick developed in Fred's group, they can switch a "tag" on a histone H3 protein. This means that up to a certain point all H3 proteins are tagged by one tag, and after the switch they are all tagged with a different tag. Using this switch we can find out where these "old" histones are several generations after the switch. This gives us insight on how the cells perserve old histones during several cycles of replication.

To quote ourselves:

To our surprise, ancestral histones accumulate near the 5′ end of long, relatively inactive genes. Using a mathematical model, we show that our results can be explained by the combined effects of histone replacement, histone movement along genes from 3′ towards 5′ ends, and histone spreading during replication. Our results show that old histones do move but stay relatively close to their original location (within around 400 base-pairs), which places important constraints on how chromatin could potentially carry epigenetic information. Our findings also suggest that accumulation of the ancestral histones that are inherited can influence histone modification patterns.

To get to these conclusions Assaf implemented a mathematical model that takes into account the processes that affect nucleosome positions, and then showed that this model can provide a good fit to the data if we consider turnover, passback of nucleosomes (from 3' to 5'), and localized dispersion during replication.  

Freiburg/Heidelberg

Just returned from a week long trip to Germany. It started by a visit to Max Planck Institute for Immunobiology and Epigenetics at Freiburg to attend a one day workshop on Chromatin. After the talks the hosts took us to a nice resto-bar where there was a long and lively scientific discussion over beer, schnitzel and white asparagus.

The next morning, it was raining, but I went on a brief walk in Frieburg's old town.

Afterwards, I continued to Heidelberg to attend the EMBL Chromatin and Epigenetics meeting. This was a four and half day meeting with a lot of interesting talks and  discussions with people. 

The meeting was held in an impressive new training center at EMBL's campus on the hills above Heidelberg. It is built as a double helix, and so there are no floors, but rather helical ramp ways all around.

I also took a half day off to go bike riding in the area and had few hours to visit the famous Schloss.

Another graduation and a new lab website

Last week Noa officially graduated. She turned in her dissertation on "Transcription Regulation Models and Their Application to Human Disease Research". She is moving on to the Weizmann Institute to work with Yaqub Hanna. 

As a parting gift before leaving us to the Weizmann, Noa created a new website for the lab (we were missing one for too long).

We will have a proper sendoff for Noa soon, although the scheduling of the event seem to be a serious challenge.

New furniture

The remaining open item in our lab renovation was furniture for the common kitchen/meeting room and for the offices. Since we were not sure about the amount of surplus budget, we left these for later stages of the renovation. 

Once the major experimental areas were finished, we started on this mini-project. As usual, the planning stage took longer than expected, and then we had to get quotes, issue a purchase order, and wait for the carpenter to make the furniture. 

Last week this process ended, and Benny our carpenter showed up to install the furniture. As part of the renovation of the kitchen he also had help in installing new kitchen top and sink. 

The end result was a brand new room with much nicer table to sit around, areas for storage, and kitchen top for the coffee machine and water dispenser. Below the counter there is a place for several refrigerators so that each group can keep its own stuff separately.

On his next visit Benny installed the office (when I was away for the retreat). The new office design looks much better and provides area to sit and work. 

CSLS Retreat

I am one of the heads of the Computer Science and Computational Biology dual-major program at the Hebrew University. The unofficial name more often used is Computer Science - Life Science (CSLS). As part of our activities we hold a yearly retreat with all the undergraduate students in the program, teachers, and some of the program graduates. 

During the retreat the third year students present their senior year project, we have some social activities, discuss the program and issues raised by students at different stages, and have a guest lecturer. 

Our guest lecturer this year was Roy Kishony from Harvard Medical Center who talked about bacteria, anti-biotics, and forces that shape they evolution of anti-bacterial resistance.

The location of the retreat is on the beach in Hof Dor (also known as Tantura, see a wikipeida article on the complex history of the place), south of Haifa, which hosts a very beautiful settings for activities. The location is northen border of the sandy beaches of southern Israel, which are formed by sand from the Nile. From here to the north there are hills of sandstone that form ragged beaches. The location was the southern-most Phoenician  city of Dor, which served as a port for various sea-routes of the Phoenician traders. They also had an active industry for collecting sea shells from which the "Royal Purple" color was manufactured (a very rare and expensive dye in the ancient world). 

Today, the natural lagons are a harbour for fishing boats and a public beach.

We finished the retreat with a short trip in Ramat Hanadiv, a park established by the Baron Edmund de Rothschild Foundation in his memory at the southern part of the Carmel mountain. This includes very nice gardens and a large area for nature conservation