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

Question 1

What is the connectivity of the brain?

Answer 1

• 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?

Question 2

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

Answer 2

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

Question 3

What are the pros and cons of cannulation

Answer 3

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

Question 4

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

Answer 4

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

Question 5

What are viral vectors?

Answer 5

• 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)

Question 6

What are viral vectors as gene therapies?

Answer 6

• 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

Question 7

What can we put in a viral vector?

Answer 7

• 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)

• ​

Question 8

What are cell-type specific promoters?

Answer 8

• 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

Question 9

What can we do with a viral vector?

Answer 9

• 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

Question 10

What are DREADDs?

Answer 10

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

Question 11

What is optogenetics?

Answer 11

• channelrhodopsins/halorhodopsins
  *

Question 12

What needs to be done outside the lab?

Answer 12

• 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

Question 13

What is science on social media?

Answer 13

• 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

Question 14

How to promote your science through social media?

Answer 14

• 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

Question 15

What is medical research crowdfunding?

Answer 15

• 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

Question 16

What was name the virus?

Answer 16

• 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

Question 17

What were other successful medical research crowdfunding projects?

Answer 17

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

Question 18

What are funding sources?

Answer 18

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