lecture 34: social media, crowd source funding and neuroscience research Flashcards

1
Q

What is the connectivity of the brain?

A
  • more than 1000 nuclei of the brain
  • cells within the nuclei are a heterogenous population
  • an average neuron has approximately 1,000 connections to other neurons
  • so how do we investigate the specific function of a brain nuclei or of sub-populations of neurons within a specific nuclei?
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2
Q

What are the pros and cons of testing lesion brain regions to investigate the brain?

A
  • region specific
  • complete ablation
  • damage to fibres of passage
  • off target effects
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3
Q

What are the pros and cons of cannulation

A
  • region specific
  • reversible
  • versatile
  • difficult to assess “normal” behaviour with chronic treatment
  • risk of infection
  • off target effects
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4
Q

What are pros and cons of using viral vectors to investigate the brain?

A
  • region specific
  • cell type specific
  • versatile
  • long term effects
  • inducible
  • affected cells easily identifiable
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5
Q

What are viral vectors?

A
  • viral vectors are modified viruses
    • lentiviruses - e.g. HIV
    • adeno-associated viruses
    • retroviruses - e.g. Moloney murine leukaemia virus
    • adenoviruses
    • herpex simplex viruses
    • pseudorabies
  • viral vectors are based on viruses
  • viral vectors are generally modified to inhibit their ability to replicate
    • viruses infect cells - can then produce more viruses
    • viral vecotrs transduce cells - cannot replicate
    • viral vectors have been selected for their low immunogenecity
  • viral vectors deliver specifically packaged genetic material
  • viral vectors have a wide range of applications
    • gene therapies
    • basic research; neuroscience, cancer, immunology etc
    • vaccines - HIV, avian influenza (H5N1)
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6
Q

What are viral vectors as gene therapies?

A
  • allows delivery of gene(s) to a specific region
  • potential treatment for inherited conditions or cancer
  • first viral-based gene therapy is now available in europe
    • glybera is an AAV based therapy targeting the genetic condition lipoprotein lipase deficiency
    • over 200 clinical trials involving viral vectors
  • animal studies examining viral vectors as a potential treatment/cure for familial hypercholesterolaemia
    • AAV vectors expressing LDLR gain-of-function variants demonstrate increased efficacy in mouse models of FH
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7
Q

What can we put in a viral vector?

A
  • genes
    • proteins
    • agonist/antagonists
    • anti-oxidants
    • fluorescent proteins
    • pharmacogenetic receptors
    • optogenetically activatable ion channels
  • promoters - PRSx8, sCAG, CMV

other regulatory elements: such as woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) or internal ribosome entry site (IRES)

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8
Q

What are cell-type specific promoters?

A
  • lentiviral transduction of the rat hypoglossal motor nucleus
  • a selection of cell type specific promoters available to put in viral vectors
    • PRSx8 - noradrenergic
    • TH - tryptophan hydroxylase
    • GFAP - glial
    • SYN - synapsin-1
    • CamKS - alpha CamKII
    • MCH - melanin-concentrating hormone
    • GAD67 - GABAergic
    • VGLUT1 -glutaminergic
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9
Q

What can we do with a viral vector?

A
  • mapping
    • LV-PRSx8-eGFP (noradrenergic) into C3
  • chronic receptor modulation
    • chronic expression of receptor agonist or antagonist
  • gene silencing
    • relaxin-3 IHC in NI
    • AAV-eGFP-miR499/relaxin-3
  • functional modulation
  • pharmacogenetics
    • designer receptors exclusively activated by designer drugs (DREADDs)
      • activation within minutes, lasts hours, 2 day wash out
      • free moving conscious animals
  • optogenetics
    • channelrhodopsins - stimulation
    • halorhodopsins - inhibition
      • switch on/off within milliseconds
      • tethered conscious animals
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10
Q

What are DREADDs?

A
  • designer receptors exclusively activated by designer drugs
  • engineered muscarinic GPCRs with no basal activity, but respond to synthetic ligand, clozapine N-oxide (CNO)
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11
Q

What is optogenetics?

A
  • channelrhodopsins/halorhodopsins
    *
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12
Q

What needs to be done outside the lab?

A
  • scientific advocacy
    • australian academy of science
    • australian society for medical research
    • australian society for neuroscience
  • scientific communication
    • visiting high schools, community groups
    • other events such as science in the cinema, brain awareness week
    • blogs
    • podcasts/radio/TV
    • articles for the public e.g. from scourge to saviour: using viruses to treat serious disease, 2000 readers and 3 comments
  • science activism
    • facebook, twitter (also weibo, pinterest etc)
      • stop the australian (anti)vaccination network
    • interactive, a conversation rather than a lecture
    • collaborative, with both scientists and non-scientists
    • anything you say or write is permanent
    • why bother?
  • science fundraising
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13
Q

What is science on social media?

A
  • e.g. facebook page stop the australian (anti) vaccination network
    • reaches up to 100,000 people a week
    • stopped (positive) media attention for the Australian Vaccination Network (now called Australian Vaccination-skeptics Network) - an anti-vaccination organisation
    • changed laws in NSW relating to health care complaints
    • consulted by Australian politicians and journalists on vaccination policy
    • two presentations at recent PHAA 14th national immunisation conference
    • review article on HPV vaccination published in a peer reviewed journal
  • twitter
    • hashtags: #science, #health, #StopAVN, #HPV, many many others
    • communities (e.g. scientists, athiests, sceptics)
    • open forum - tweets can’t be removed except by the original account
    • gives access to people who may be inaccessible through other methods
  • why bother?
    • passionate about a scientific topic
    • understand community views on a topic
    • not as time intensive as blogs/podcasts etc
    • great way to collaborate
    • promote your own research
  • e.g. hawkes (the lecturer)
    • adverse events as a result of chiropractic treatment: lack of a reporting system hinders informed health decisions and improvement of practice
    • pharmacological examination of TCM should be evidence-based
    • answering human pappilomavirus concers; a matter of science and time
    • research trends in evidence-based medicine: a joinpoint regression analysis of half a century of publication data
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14
Q

How to promote your science through social media?

A
  • e.g. paper: answering human papillomavirus vaccine concerns; a matter of science and time
  • journal impact factor of 2.07 (infectious agents and cancer)
  • open access journal
  • promoted it on Facebook and twitter
  • accessed 15,500 times since june, 2013
  • 6th most accessed article for the journal
  • twitter audience of up to 910,000
  • cited by a leading HPV research group
  • twitter as a research tool in itself:
    • HPV vaccination has the potential to reduce global deaths from cervical cancer by as much as two thirds (url) vs
    • lead developer of HPV vaccines comes clean warns parents and young girls it’s all a giant deadly scam
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15
Q

What is medical research crowdfunding?

A
  • success rate of 50-60%
  • small amounts: ~$5,000 - $30,000
  • 2-3 months time span (~1-2h per day)
  • growing number of platforms; pozible, thinkable etc
  • over 30 crowdfunding research projects in Australia
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16
Q

What was name the virus?

A
  • goal: to raise $10,000 in order to make 4 new viral vectors, in 50 days
  • online - donations from $1
  • between october 20th and December 9th, 2013
  • only get money if you reach your target ($10,000)
    • so if you raise $9,000 you get nothing
  • rewards
    • $50 - postcard with a viral vector image
    • $100 - a personally designed virus
    • $2500 - you get to name the virus
  • how they promoted the project
    • facebook and twitter
    • 322K followers on twitter, 34.3 K tweets
    • name to go viral, for a fee - herald sun oct 20th
    • ABC breakfast - dec 3rd
  • raised 129% of target
  • reached $10,000 six days early
  • had 3 people “name the virus:
    • pSLING
    • pUNCHINGMAN
    • pMyra
17
Q

What were other successful medical research crowdfunding projects?

A
  • drug-free brain treatments
  • mightymaggots vs fleshnom bugs
  • faith in neuroscience
  • hips 4 hipsters
18
Q

What are funding sources?

A
  • australian government: national health and medical research council (NHRMC)
  • crowdfunding
    • crowdfunding for medical research picks up pace - the lancet article