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My trip to the Hong Kong Eye Hospital

Sunday, January 29, 2012

I was invited and supported by the Purdue Research Foundation (PRF) International Travel Grant to give a Plenary Lecture at the Symposium on Biology of Ophthalmology 2011 which took place in the Hong Kong Eye Hospital from 11-13th December 2011. The event was organized by the Department of Ophthalmology and Visual Sciences at the Chinese University of Hong Kong (CUHK), a leading eye research center in Asia.

Some participants at the Symposium on Biology of Ophthalmology 2011

 

The symposium covers a wide variety of topics from clinic research, ophthalmic imaging, genetic screen to very basic eye research. Together with Dr. Motokazu Tsujikawa from Osaka University Ophthalmology, we shared our vision on studying  retinal degeneration using zebrafish. Dr. Liyun Zhang, currently a Charles Kelman MD Scholar of the International Retinal Research Foundation whom works in my laboratory, also shared her future plans on studying disease-causing gene network of fish model of human retinal degeneration. It is really impressive that many physicians can perform top clinical service and yet can spare time to do high-quality research.

Both Liyun and I chaired sessions on various aspects of exciting ophthalmic research from different research groups, and through these interactions,  we have met new and old friends, including Dr. Rosa Chan from City University of Hong Kong who is studying computational modeling of brain activity, a group of very dedicated and accomplished scientists including Drs Yan, Hou and Zhou from the Eye Hospital at Wenzhou Medical College where I also visited during the trip, friends from Osaka Ophthalmology including Drs. Kohji Nishida, Yasushi Ikuno and Motokazu Tsujikawa, Dr. Carol Cheung from Singapore, Dr. Richard Choy and Gary Yam, among many others from CUHK and friends from the Joint Shantou International Eye Center (JSIEC) at Shantou University, etc.

Right after the symposium, I led a 2-day workshop on “Frontiers in human genetics and eye research” with about 15 students from several locations. My goal was to help students who have only been focused on a narrow genetic aspect and/or clinical aspects of ophthalmology to put their knowledge on a wider perspective. Each day we read and presented a paper about either human genetics and eye research using zebrafish model in depth. This time we discussed two papers:

  1. Zhong Q, Simonis N, Li QR, Charloteaux B, Heuze F, Klitgord N, Tam S, Yu H, Venkatesan K, Mou D, Swearingen V, Yildirim MA, Yan H, Dricot A, Szeto D, Lin C, Hao T, Fan C, Milstein S, Dupuy D, Brasseur R, Hill DE, Cusick ME, Vidal M. Edgetic perturbation models of human inherited disorders. Mol Syst Biol. 2009;5:321. Epub 2009 Nov 3. PubMed PMID: 19888216; PubMed Central PMCID: PMC2795474.
  2. Kay JN, Roeser T, Mumm JS, Godinho L, Mrejeru A, Wong RO, Baier H. Transient requirement for ganglion cells during assembly of retinal synaptic layers. Development. 2004 Mar;131(6):1331-42. Epub 2004 Feb 18. PubMed PMID: 14973290.

I was really impressed with many of them who were thinking about the new ideas and tools in a critical manner and was very engaged in a lively discussion.

It was a gratifying experience to interact with and see many students fro the Asia region who are laying down the foundation for and conducting great research! Kudos to the organizers including Drs. Calvin Pang and Chris Leung from the CUHK for putting together an excellent conference program to make the whole trip possible!

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Promising results from the first humal trial of treating incurable eye diseases with embryonic stem cells

Wednesday, January 25, 2012

From Washington Post:

For the first time, an experimental treatment made from human embryonic stem cells has shown evidence of helping someone, partially restoring sight to two people suffering from slowly progressing forms of blindness.

In short, the authors of this study that is just published in Lancet differentiated human embryonic stem cells (hESC) into retinal pigment epithelium (RPE), a key eye tissue that is often affected in retinal degeneration. Then, they transplanted these RPE cells into two patients suffering from Stargardt’s disease and age-related macular degeneration. The purpose of the trial was to find out whether this procedure is safe. Interestingly, there was a pleasant surprise that both patients seem to have some improvements in eye sight. While there is still a lot to do before stem cells therapy will become widely applicable as a general treatment, this finding is an encouraging first sign.

Reference

Embryonic stem cell trials for macular degeneration: a preliminary report [Lancet][pdf]

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2012-01-14 new articles we read this week

Saturday, January 14, 2012

Retinal Development

  1. Kwan KM, Otsuna H, Kidokoro H, Carney KR, Saijoh Y, Chien CB. A complex choreography of cell movements shapes the vertebrate eye. Development. 2012 Jan;139(2):359-72. PubMed PMID: 22186726.
  2. Morgan JL, Soto F, Wong RO, Kerschensteiner D. Development of cell type-specific connectivity patterns of converging excitatory axons in the retina. Neuron. 2011 Sep 22;71(6):1014-21. Epub 2011 Sep 21. PubMed PMID: 21943599; PubMed Central PMCID: PMC3184549.

Stem cells

  1. Salero E, Blenkinsop TA, Corneo B, Harris A, Rabin D, Stern JH, Temple S. Adult Human RPE Can Be Activated into a Multipotent Stem Cell that Produces Mesenchymal Derivatives. Cell Stem Cell. 2012 Jan 6;10(1):88-95. PubMed PMID: 22226358.
    • Commentary: Trounson A, Grieshammer U. Chimeric Primates: Embryonic Stem Cells Need Not Apply. Cell. 2012 Jan 4. [Epub ahead of print] PubMed PMID: 22225613.
  2. Phanstiel DH, Brumbaugh J, Wenger CD, Tian S, Probasco MD, Bailey DJ, Swaney DL, Tervo MA, Bolin JM, Ruotti V, Stewart R, Thomson JA, Coon JJ. Proteomic and phosphoproteomic comparison of human ES and iPS cells. Nat Methods. 2011 Sep 11;8(10):821-7. doi: 10.1038/nmeth.1699. PubMed PMID: 21983960.

Genetics

  1. Zhang F, Vierock J, Yizhar O, Fenno LE, Tsunoda S, Kianianmomeni A, Prigge M, Berndt A, Cushman J, Polle J, Magnuson J, Hegemann P, Deisseroth K. The microbial opsin family of optogenetic tools. Cell. 2011 Dec 23;147(7):1446-57. PubMed PMID: 22196724.
  2. McMahon MA, Rahdar M, Porteus M. Gene editing: not just for translation anymore. Nat Methods. 2011 Dec 28;9(1):28-31. doi: 10.1038/nmeth.1811. PubMed PMID: 22205513.
  3. Zhao S, Ting JT, Atallah HE, Qiu L, Tan J, Gloss B, Augustine GJ, Deisseroth K, Luo M, Graybiel AM, Feng G. Cell  type–specific channelrhodopsin-2 transgenic mice for optogenetic dissection of neural circuitry function. Nat Methods. 2011 Sep;8(9):745-52. PubMed PMID: 21985008; PubMed Central PMCID: PMC3191888.

Genomics

  1. Kalhor R, Tjong H, Jayathilaka N, Alber F, Chen L. Genome architectures revealed by tethered chromosome conformation capture and population-based modeling. Nat Biotechnol. 2011 Dec 25;30(1):90-8. doi: 10.1038/nbt.2057. PubMed PMID: 22198700.
    • Commentary: Misteli T. Parallel genome universes. Nat Biotechnol. 2012 Jan 9;30(1):55-6. doi: 10.1038/nbt.2085. PubMed PMID: 22231096.
  2. Lam HY, Clark MJ, Chen R, Chen R, Natsoulis G, O’Huallachain M, Dewey FE, Habegger L, Ashley EA, Gerstein MB, Butte AJ, Ji HP, Snyder M. Performance comparison of whole-genome sequencing platforms. Nat Biotechnol. 2011 Dec  18;30(1):78-82. doi: 10.1038/nbt.2065. PubMed PMID: 22178993.
  3. Mercer TR, Gerhardt DJ, Dinger ME, Crawford J, Trapnell C, Jeddeloh JA, Mattick JS, Rinn JL. Targeted RNA sequencing reveals the deep complexity of the human transcriptome. Nat Biotechnol. 2011 Nov 13;30(1):99-104. doi: 10.1038/nbt.2024. PubMed PMID: 22081020.

Systems Biology

  1. Young JW, Locke JC, Altinok A, Rosenfeld N, Bacarian T, Swain PS, Mjolsness E, Elowitz MB. Measuring single-cell gene expression dynamics in bacteria using fluorescence time-lapse microscopy. Nat Protoc. 2011 Dec 15;7(1):80-8. doi: 10.1038/nprot.2011.432. PubMed PMID: 22179594.
  2. Dutkowski J, Ideker T. Protein networks as logic functions in development and cancer. PLoS Comput Biol. 2011 Sep;7(9):e1002180. Epub 2011 Sep 29. PubMed PMID: 21980275; PubMed Central PMCID: PMC3182870.

Neuroscience

  1. Kralj JM, Douglass AD, Hochbaum DR, Maclaurin D, Cohen AE. Optical recording of action potentials in mammalian neurons using a microbial rhodopsin. Nat Methods. 2011 Nov 27;9(1):90-5. doi: 10.1038/nmeth.1782. PubMed PMID: 22120467; PubMed Central PMCID: PMC3248630.
    • Commentary: Looger LL. Running in reverse: rhodopsins sense voltage. Nat Methods. 2011 Dec 28;9(1):43-4. doi: 10.1038/nmeth.1817. PubMed PMID: 22205516.
  2. Pan YA, Choy M, Prober DA, Schier AF. Robo2 determines subtype-specific axonal projections of trigeminal sensory neurons. Development. 2012 Feb;139(3):591-600. Epub 2011 Dec 21. PubMed PMID: 22190641; PubMed Central PMCID: PMC3252355.
  3. Nishimoto S, Vu AT, Naselaris T, Benjamini Y, Yu B, Gallant JL. Reconstructing visual experiences from brain activity evoked by natural movies. Curr Biol. 2011 Oct 11;21(19):1641-6. Epub 2011 Sep 22. PubMed PMID: 21945275.
  4. Cavallari N, Frigato E, Vallone D, Fröhlich N, Lopez-Olmeda JF, Foà A, Berti R, Sánchez-Vázquez FJ, Bertolucci C, Foulkes NS. A blind circadian clock in cavefish reveals that opsins mediate peripheral clock photoreception. PLoS Biol. 2011 Sep;9(9):e1001142. Epub 2011 Sep 6. PubMed PMID: 21909239; PubMed Central PMCID: PMC3167789.

Vision

  1. Kingdom FA. Binocular vision: the eyes add and subtract. Curr Biol. 2012 Jan 10;22(1):R22-4. PubMed PMID: 22240475.

Education

  1. Vanderford NL. Broadening PhD curricula. Nat Biotechnol. 2012 Jan 9;30(1):113-4. doi: 10.1038/nbt.2091. PubMed PMID: 22231111.

Medical Research

  1. Reed JC, White EL, Aubé J, Lindsley C, Li M, Sklar L, Schreiber S. The NIH’s role in accelerating translational sciences. Nat Biotechnol. 2012 Jan 9;30(1):16-9. doi: 10.1038/nbt.2087. PubMed PMID: 22231085.
  2. Hudson KL. Genomics, health care, and society. N Engl J Med. 2011 Sep 15;365(11):1033-41. Review. PubMed PMID: 21916641.
  3. Devi S. Lasker Foundation honours malaria researcher. Lancet. 2011 Sep 24;378(9797):1129. PubMed PMID: 21969956.

Zebrafish

  1. Thummel R, Bailey TJ, Hyde DR. <em>In vivo</em> Electroporation of Morpholinos into the Adult Zebrafish Retina. J Vis Exp. 2011 Dec 27;(58). pii: 3603. doi: 10.3791/3603. PubMed PMID: 22231802.
  2. Lawrence C. Advances in zebrafish husbandry and management. Methods Cell Biol. 2011;104:429-51. Review. PubMed PMID: 21924176.

Evolution

  1. Pearlman SM, Serber Z, Ferrell JE Jr. A mechanism for the evolution of phosphorylation sites. Cell. 2011 Nov 11;147(4):934-46. PubMed PMID: 22078888; PubMed Central PMCID: PMC3220604.

 

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An interesting story about Eric Lander

Friday, January 13, 2012

Rick Friedman for The New York Times

From New York Times:

CAMBRIDGE, Mass. — His Ph.D. is in pure mathematics, in a subfield so esoteric and specialized that even if someone gets a great result, it can be appreciated by only a few dozen people in the entire world. But he left that world behind and, with no formal training, entered another: the world of molecular biology, medicine and genomics.

Read the whole article “Power in Numbers” here.

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The making of a machine to test vision of zebrafish larvae

Friday, January 6, 2012

We have recently begun to work on a project that requires us to find out whether a zebrafish larva can see or not. To this end, we have built a small machine to check whether the larvae show a visual behaviour called the optokinetic response (OKR).

This video shows the OKR machine, which is essentially a drum with black and white stripes that the rotating direction is controlled by a motor.

 

The fish larvae will be immobilized in thick solution in a Petri dish, which will be put inside the drum. The larvae with normal vision will be able to track the stripe rotation and move their eye balls. In this video, the bottom larva shows a normal OKR, while the top one does not show an OKR. It does not show an OKR because it is a blind mutant. An air bubble is put on the left to reflect the direction of the stripe movement.

 

During the process of fabricating this machine, we had come across with another cheaper way to do the same thing. There is a type of ancient Chinese lantern that part of outside drum will move due to heat convection generated by the light (A picture can be found in this Chinese article). We bought a contemporary version that the moving drums are driven by a motor. The type that we bought has the moving mechanism for rotating in opposite direction. We then took apart the lantern and used the moving mechanism to drive the opposite rotating stripes. See the following video for the moving mechanism of this alternative version of OKR.

 

Even though it is not perfect, it works! The most amazing part is the difference in the cost of fabrication.

  • The OKR machine made from Chinese Lantern: ~ $US 3 (for buying the Chinese Lantern)
  • The OKR machine that is made as shown in the first video: ~$US 150 (for materials) + ~$600 (for labor) = ~ $800 (and that does not include the controller box) !!!
  • A turnkey solution from a company costs > $40,000!

That is actually another example of the difference in the cost structure in doing research between the East and the West!

I also had a lot of fun sourcing other cheap parts for the final setup. For example, I have bought a very decent eye-piece camera for less than $40 (the price seems to have gone up a bit since then… but it is still very cheap) to capture the video of larval eye movement as shown in the second video. I have also bought a very economical ring light from AmScope for less than $60 for illuminating the drum area finally.

We are going to use this assay to identify fish with eye problems and then characterize the underlying molecular defects. That will help us study and find cures for the same diseases in human.

 

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Generation of Chimeric Monkey

Thursday, January 5, 2012

Today there is an article published in CELL about the generation of chimeric monkey. Unlike the traditional way for generation of chimeric mouse for making transgenic animal that can utilize pluripotent stem cells or inner cell mass, the process in primates requires the usage of totipotent cells at a much earlier stage – 4-cell stage. The authors could aggregate these early embryos and generate chimera. See a simple and good news coverage from the BBC for further discussions of the importance.

Adopted from the journal website

References

  1. Tachibana M, Sparman M, Ramsey C, Ma H, Lee HS, Penedo MC, Mitalipov S. Generation of Chimeric Rhesus Monkeys. Cell. 2012 Jan 4. [Epub ahead of print] PubMed PMID: 22225614.
    • Commentary: Trounson A, Grieshammer U. Chimeric Primates: Embryonic Stem Cells Need Not Apply. Cell. 2012 Jan 4. [Epub ahead of print] PubMed PMID: 22225613.

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My trip to the Eye Hospital at Wenzhou Medical College

Monday, January 2, 2012

A warm Chinese-style welcoming at the entrance!

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

I recently visited the Eye Hospital at Wenzhou Medical College, where they have very good research infrastructure that has integrated various aspects of basic and clinical ophthalmology research together. I gave two talks over there and had a great interaction with everyone. I did not get a chance to take many pictures but here are a few snapshots of some interesting things that I have seen. One particularly impressive setup in their group is a large meeting and relaxing area that is right next to the research laboratories. Conducting a successful research is about communication and conversation; merely having good equipment is not enough, it is crucial to have effective interaction between research members at all levels. With a wonderful atmosphere as such, I can totally imagine the colleagues from Wenzhou will have very fruitful and exciting interactions. Indeed, the teachers there are very sincere and down-to-earth, and the students are very enthusiastic in learning new ideas. Many of them were in fact courageous enough to ask questions and discussed their ideas during and after my lectures. This is really contradictory to the stereotype of many quiet and obedient Asian students. No wonder their group has a very rigorous research and education program.

A nicely decorated balcony for students to take a break or spend time thinking about research!

A well lit meeting area for research group members to interact. I had an enjoyable lunch and conversation with several students here.

It is really gratifying to see that there are many Chinese Institutes conducting good research. When the West is undermining their good research infrastructure in the midst of a poor economy, it is not surprising that the East is going to catch up and will lead the scientific research in the near term future.

A glimpse of the prosperous Wenzhou city from my hotel room.

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How Doctors (Physicians) Die

Thursday, December 29, 2011

How Doctors Die – It’s Not Like the Rest of Us, But It Should Be

A deep article written by Ken Murray about how some physicians and patients would opt for less or no treatments when they encounter terminal illness.

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2011-12-03 New articles we read this week

Saturday, December 3, 2011

Medicine

There seems to be a new effective drug for Cystic Fibrosis!

  1. Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Dřevínek P, Griese M, McKone EF, Wainwright CE, Konstan MW, Moss R, Ratjen F, Sermet-Gaudelus I, Rowe SM, Dong Q, Rodriguez S, Yen K, Ordoñez C, Elborn JS; VX08-770-102 Study Group. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011 Nov 3;365(18):1663-72. PubMed PMID: 22047557.
    • Commentary: Davis PB. Therapy for cystic fibrosis–the end of the beginning? N Engl J Med. 2011 Nov 3;365(18):1734-5. PubMed PMID: 22047565.
    • News coverage: “Cystic Fibrosis Drug a Game Changer?” from WebMD.com
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Occupy Science

Thursday, December 1, 2011

This is a cross post from a discussion thread on my facebook, after the UC Davis pepper spray incidence. There are interesting ideas that are worthwhile to think further. It is also interesting to see that there are scientists joining the actual Occupy protests… um..  I still think the problem is not merely the lack of funding, but is a fundamental issue of the business model for the contemporary scientific research.

—-

Fai: After seeing what is happening in the Occupy Wall Street movement, especially the very recent episodes at UC Davis, I cannot stop thinking about the resemblance between the current social issues and the problems that sincere research scientists at all levels are facing. In fact, part of the problems is caused by these social issues related to business and government policy; and many of us can easily tell a few personal stories. We have been trained to be critical of our work, why can we not be critical about the system as well? For example, if we were allowed to redesign our university and research system, what should we do to ensure that we will build a sustainable system for the society, students and scientists? I am intrigued in hearing from my friends who have been contributing in the field across the world.

Abel Chun: But the fact seems to be that politics rules the world. Like in HKU, there’re many good scientists for life science but they’re “workers” under the command of professors who come from Medicine, not PhD. After all, we have to apply for grants to survive but those who review the grants are bearing lot of power, managerial levels, and even some so-called scientists (eg. from ITF). If we write a grant proposal simply for “understanding the nature”, U will never get a penny. But if U say your research can lead to drug development, can make big $, ok, here U go.

Albert Hui:  Changes only ever happen top-down. See what George Soros did to advance his open society movement? First make big money.

Winnie Tong: We are too specialised. Research training nowadays is very concentrated in speacilised techniques for specific narrow subject area and often one is pretty much stuck within one research area. It just limits our choices for jobs and power for negotiation. I knew some people would not mind being ‘workers’ for life. What they hate is the job insecurity every 2-3 years for all their working life. Even the universities offer some help at the end of each contract, usually it’s just putting you on a list for other research groups. You will be lucky if they are looking for your specific skill set, otherwise it’s good bye and good luck after a few months. If I can redesign the university and research system, everyone should have at least a few weeks of sabbatical time to actually work in a completely different research area.

Fai: Abel: it’s the same (censored) everywhere.

Fai: Albert: I always want to be a philanthropist.

Fai: Winne: that is indeed the core problem! Many good-hearted, intelligent people did not realize that the business model is actually a contest. And that is often not taught explicitly at school. I don’t think merely providing time to learn new skills without a wholesale improvement if the business model can alleviate the frustration of most participants.

Fai: Abel: and you would agree much of the creativity of the whole community is wasted on irrelevant stuff because of the business model.

Winnie Tong:  True. But it’s something that can be done on our end now, at least if you have a good boss. Like what google does, allowing 10% time for blue-sky development. And say two weeks is like a long conference time, long enough to actually gain some hands on experience and network to other research groups. 1-3 days is just way too short. You tend to forget and less chance to touch any buttons. It would be much easier, say, instead of small little pots of funding within individual research groups, perhaps some of it can go to a centralised place. This pool of fund can be use to hire some more permenant research staffs, who can rotate between labs and groups. This is a bit like the industry where the same scientists may be put in several different projects instead of just one. This way you can utilise the avaliable man power better for more urgent projects. It will be great if the University and funding bodies can think of a way to adopt some of this industrial approach, but that probablywould mean PIs will have to let go of their control over their own funding and it is unlikely to happen.

Fai: Google’s approach is nice and is indeed the approach for many postdocs and graduate students. You always want to try something new. However that may not be for every one. The idea for centralizing and rotating staff is interesting, but I can imagine strong resistance at the administration level. The current model is project based and the school earns money from the government by getting support for new projects. Since staff who can perform a specific skill is related to a project, it is a budgeting nightmare to figure out how to rotate some core people around between different projects. It does require a whole new way of funding and administration. In addition, given the expensive staff and the financial situation, having centralized staff may not be a sustainable solution.

Winnie Tong: I think what’s demaging is that many people are only hired and involved in a single project. I think we can start small, say, two PIs share their research staffs between their projects. If each PI has one full-time staff, it means there will be two full-time people for two projects.

Fai: Without a concomitant change in the system, this bottom-up approach can be problematic. Project time will vary, who is going to pay for the staff when one project is terminated? Also the resolution on the staff time can also be problematic… this is the fundamental dilemma between the award-based system and the desire of many who would opt for a stable life.

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