Tracing Neuronal Circuits

    19/04/2014

    One of the hottest topics in neuroscience today lies in the visualization of neuronal connectivity in order to fully understand the nervous system. A variety of neuronal networks are connected through synapses that convey electrical signals between each system of the CNS and PNS. Specific groups of neurons populate different areas of brain and spinal cord architecture, giving rise to motor, sensory, behavioural and cognitive functions. This recent paper from the George Smith lab, by my colleague Dr. Ying-peng Liu, demonstrates a new method of tracing such a neuronal network, specifically to study regenerating axons in the spinal cord of rat models.

     

    PlosOne

     

    He essentially injects self-complementary Adeno-Associated Virus (sc-AAV-2), tagged with GFP into different nuclei of the brain or the dorsal root ganglia in order to label motor and sensory fiber tracts. Neuronal cell bodies and axons fluoresce bright green three weeks after injection, following the expression of the sc-AAV-2. Any damage or lesions to the tract can be easily visualized since the virus is anterogradely transported along the axon.

     

    YPFig1

    Schematic shows the pathway traced by injecting the sc-AAV-2 virus into the sensorimotor cortex to trace the corticospinal tract (A), injecting into the Raphe Nucleus to trace the rubrospinal tract (B) and injecting into the dorsal root ganglia to trace the sensory motorneurons of the dorsal column (C)

    What makes this sc-AAV-2 tracer different from previous anterograde tracers, such as BDA or CTB or single stranded AAV is that transduction efficiency is so high and it is so specific to large cell body neurons. It is clearly demonstrated by this paper that this is a faster, more effective way to visualize damaged axons. The fact that AAV plasmids can be cloned to carry therapeutic genes is also a bonus since it allows us to inject the green fluorescence tag together with genes of interest in one virus and study their distributions in the animal after transfection.

     

    YPFig9

    This figure shows a lesion cavity in the cervical spinal cord, labeled by GFAP (BLUE), the corticospinal tract labeled by BDA tracer (RED) and the sensory axons labeled by sc-AAV-2 GFP (GREEN)

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      Pint Of Science

    30/03/2014

     

    Here is a fun, novel, science-promotion event taking place called "Pint of Science". While many may consider drinking beer at the pub as just another way to drown their miseries over failed experiements, this event has in fact blossomed into a nationwide festival in the UK comprised of a series of TED-style lectures given by experts in biology, physics, earth sciences and mathematics. It is the brain child of a few London scientists, some from my old alma mater, King's College London, devised to engage scientists with the public in interesting discussions over a few beers. The American version of Pint of Science will kick-off in May in 4 cities spanning the US. I have been recruited by Dr. Parmvir Bahia, the US coordinator, to host the first event in Philadelphia. Despite my initial reservations about America lacking the "drinking culture" that the Brits adamantly adhere to, we are pretty sure we can pull this off!

    Any scientists who want to speak in May in Philadelphia, Tampa, Chicago or San Diego, or anyone wishing to volunteer to help organize the event should write to contact@pintofscience.us.

     

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      SfN Meeting Nanosymposium

    22/01/2014

    I was fortunate enough to be selected for one of the SfN Nanosymposium talks last year in San Diego. This one was hosted by Richard Zigmund for the final neuro-regeneration focussed session. The talk went well and two or three people were able to ask questions at the end. This gave me good feedback and I even met some people who wanted to collaborate.

    Nanosymp

    However, this all took place on a bright, sunny southern California day, at the end of a 5 day conference, when most people were preparing to or had already departed from the meeting. I stood in a small, darkened meeting room and gave a 10 minute spiel about my research to around 50 people who sat scattered in a small-ish auditorium room that easily had a capacity for up to 400 people. The hollow darkness of the meeting room left much to be desired and the fatigue from the long meeting was clear on most people's faces. Next time I sign up for a talk or poster session, it should be in the earlier days of a conference.

    Here is an excerpt of the first few minutes from my Nanosymposium talk at the SfN Meeting last year in San Diego:

     

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      The Brain Initiative

    06/01/2014

    Amid the doom and gloom of last year's sequestration announcements, Obama promised to inject $1 billion into mapping the human brain as part of the Brain Initiative. The aim is to build a "Google Maps" version of the human brain, in order to aid research for the treatment of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. This also coincided with the launch of the European Human Brain Project, as a way to build international collaboration.

    Here is a sleek, clean and cool video patched together by the NY Times about the work of one Deanna Barch, a superstar psychology professor from the University of Washington, St Louis, funded by this initiative:


    The fancy new European human brain project's website:

    HBP

    The Brain Initiative funding will be distributed to the NIH, NSF and other defence research bodies. I'd like to add that $1 billion is a drop in the ocean compared to the $38 billion agreed cuts in "discretionary spending", but in the world of basic research we will have to get whatever is given.

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      Two more online courses done!

    15/12/2013

    I have completed two more online introductory courses on Coursera: Virology 1: How Viruses Work and Calculus One

    Virology 1 was quite easy for me because of the heavy focus on basic molecular biology. Now I am thirsty for the follow-up to this course, by the famous Vincent Racaniello of Columbia, and learn about the pathological effects of different viruses.

    Calculus One was tricky for me. However this has been the most enjoyable course I have ever taken! The two main teachers, Bart Snapp and Jim Fowler of Ohio State U. are absolute geniuses when it comes to explaining derivatives and integration. Hats off to them! I am truly inspired to, quoting Bart Snapp, "Do more math". Just hope I have time to do Calculus Two in future.

     

    Cert2

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      Shriners Fellowship Awarded!

    15/12/2013

    In the middle of October I submitted the Shriners Foundation application, our internal funding agency. My application has now been reviewed and approved. I am set to work for three more years at the Shriners Center at Temple University. Now comes the hard part of making sense of the data and publishing it!

    I will take this as a victory to end a year of high stress and anxiety inside the world of academic biomedical research. The road ahead will be tough, but at least, there is now a road.

    Shriners

     

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      One week until SfN

    02/11/2013

    There are 7 days left until the Neuroscience Meeting in San Diego. It's time to wrap up those experiments, get the posters printed and finish preparing those powerpoint presentations before the meeting. I have my badge ready: as in previous years, I am going as a student!

    Badge

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      Shriners Fellowship Grant Submitted

    02/11/2013

    In October, I completed my second postdoc fellowship grant submission to the Shriners Hospitals for Children. This was an "internal" fellowship, awarded by the organization that originally founded our department, which was available for only TWO postdoctoral applicants in our department for this cycle of 2013. This grant is based on the same hypothesis and series of studies that I proposed to the PVA.

    There were great challenges submitting this one due to technical glitches and server crashes with the Altum Proposal Central website on the date of the deadline! However, we managed to squeeze the proposal package through the net. Awards have previously been given competitively to principle investigators and postdoc fellows in our center. This year, we will keep our fingers crossed for more!

    Shriners founded, supports and pays for most of the research in our center at Temple Univeristy, under the direction of Michael Selzer. But we are also affiliated with Temple University.

    Read more about Shriners funded research here: http://www.shrinershospitalsforchildren.org/Research.aspx

    Shriners

    A video by the Shriners Research Center in Portland OR:


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      Fellowship Grant Submitted

    30/08/2013

    This week I completed my fellowship grant submission to the Paralyzed Veterans of America (PVA) Research Foundation in a bid to continue my work at Temple University and at the Shriners center for regeneration. The grant essentially proposes to study axonal regeneration by looking at how drugs can affect microtubule stability. Though this is a small grant asking for just $100,000 over two years, getting it would mean the difference between staying on in the lab or packing my bench up and leaving. The fact of the matter is, I will be dependent on having a PI who can sponsor me AND a funding body that can sponsor my experiments. Of course we in the lab are busy submitting more grants right now.

    The PVA is a charity dedicated to providing care, rehabilitation and civil rights for injured veteran soldiers. Here is one way you can donate to them - by offering your old car to a wounded warrior:

    WforW

    Last year they secured over $250 million for veterans benefits directly from the US government - not an easy feat. Each year they award between 6 to 12 grants to biomedical and clinical research, only a fraction of which are fellowships for postdoctoral fellows. This year their funding may be much lower due to many factors, not helped by Sequestration. Right, time to write another grant!....

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      SfN Meeting Itinarary is online

    23/08/2013

    This year's SfN Meeting in San Diego will be a blast. It will also be a welcome respite from work allowing me and my co-workers to reflect on the progress we have made over the year and the great challenges we are facing. The itinerary planner and abstract browsing is now posted online. Here is my sesssion detail:

    SfN Nano

    You can now peruse the planner for abstracts that interest you here if you want to plan ahead. My nanosympsium talk has been placed on the dreaded last day in the afternoon, when traditionally many people leave for their flights! However those who have not left the meeting early will be treated to a short talk by me about the research I am doing.

    Four people from our lab are attending this meeting with three of us all presenting on Wednesday. We have booked our flights and hotels already. This gives us ample time to plan sight-seeing activities in the San Diego bay area and make contact with people we want to see.

     

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      Completed Online Courses

    06/08/2013

    I recently completed two courses with Coursera online, joining the massive open online course (MOOC) revolution that is sweaping through the education world. I finished a Microeconomics course and a Systems Biology course. Systems biology was challenging because of the wide range of mathematics, biology and physics topics involved. Microeconomics was useful for an outsider like me with limited financial knowledge.

    Cert1

    I certainly plan on taking a few more of these courses, considering they are essentially FREE. You can also pay for "Signature Track" which allows you to earn a verified electronic certificate after successfully completing a degree and enables you to share it with employers online.

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    14/07/2013

    Here is a video which sums up systems biology in the context of the world today:

     

    Systems Biology essentially aims to study the interactions between all types of biological information from DNA, RNA, proteins, metabolites, transcription factors, kinases, cells and organs to understand physiological functions. Some of its methods include datamining large miroarrays datasets and analyzing protein interaction networks to understand how complex organs function and how diseases result from mutated genes. Thus systems biology lends itself well towards the study of neuronal function, brain cognition and spinal cord injury. In fact plenty of research has already been done on brain networks using systems biology - just take a look at this Frontiers in Neuroscience paper and this feature in Nature Reviews.

    To further emphasize the growing importance of systems biology, we have only to look at how "Big Data" is becoming increasingly sought after by other industries and careers, including financial companies and the military. We can even think of its importance in light of the recent Edward Snowden leak about the NSA's secret spy programs, since many of the tools used to analyze networks in systems biology may be employed by the NSA to analyze how people connect/communicate to one another.

    I have recently studied and completed an online course with Coursera on Systems Biology. As a massive open online course (or MOOC) this has been a challenging and refreshing way to learn about a complex, developing area of research. Over the 6 weeks of lectures, taught by a Mount Sinai group under Ravi Iyengar, I have discovered one of key ingredients that has been missing in my research training - systems integration at multiple biological levels. This, dare I say it, is one of the many deficiencies of PhD training programs in basic biomedical research that will need to be reformed in the future (and quickly, considering the upcoming sequestration).

    Image of a complex insulin–Jak/STAT–TGFb network (Chassey et al., 2008) in Hep C virus.

 

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Retiring the Mouse Model Gold Standard

Brexit Britain I weep for you

Surgeries

Seven Years in Visaland

Photo Website

Restimulating the Party

Start Talking Science

A Journey into my Genome

Patent Law IX, The Limits of Biotech Patents

Patent Law IX, The Longest Patent Extension Battle

Patent Law VIII, Invasion of Patent Trolls into Biotech

Patent Law VII, DTC Genomic Testing

Patent Law VI, Supreme Court and Laws of Nature

Patent Law V, The Dark Web

Patent Law IV, Gaming the Hatch-Waxman Act

Patent Law III, The Brave New World of Biosimilars

Patent Law II, The Everlasting Patent

Patent Law I, CRISPR-Cas9

FDA Law Intro

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Neuroscience Drugs

Locked-in Syndrome

SCI scar Inhibitor

Google-Calico

p-Hacking

Immigration

Neuropathic Pruritus

Mitochondrial Disease, 3 parent baby

Multiple Sclerosis and Axon Injury

Pint of Science Philadelphia

The Mesoscale Connectome

Tracing Neuronal Circuits

Pint of Science

Nano-symposium

The Brain Initiative

Two more online courses done

Fellowship Awarded

One week

Shriners Fellowship

PVA Fellowship

SfN Itinerary

Online Course Certificates

Systems Biology