Outreach activity at SIB
&
Drug Design workshop
Swiss-Prot meeting 19.12.2017
Outreach activities at SIB:
o What
o Where / Who
o Outreach ‘Uniprot’
o Funding o Next events
Drug Design workshop
Menu
Outreach activities at SIB:
o What
o Where / Who
o Outreach ‘Uniprot’
o Funding o Next events
Drug Design workshop
Menu
Outreach activities at SIB: what
3 websites, several workshops:
ChromosomeWalk.ch
education.expasy.org/bioinformatique
(metagenomic pizza (BLAST@UniProt), bioinformatics, genome and genetic disease (BLAT), …)
www.atelier-drug-design.ch
SIB: www.sib.swiss/bioinformatics-for-all
UNIGE: www.unige.ch/ressourcespedagogiques UNIGE: scienscope.unige.ch/
CH initiative: educaMINT.ch
EU initiatives: www.Scientix.eu, science on stage (STEM education)
Outreach activities at SIB: www.sib.swiss/bioinformatics-for-all
scienscope.unige.ch/
Outreach activities at SIB:
o What
o Where / Who
o Outreach ‘Uniprot’
o Funding o Next events
Drug Design workshop
Menu
Outreach activities at SIB: where / who
o Popular events (public at large) o Events around the classroom o Training high-school teachers o Career guidance (OFPC)
Training high-shool teachers
(The American School in Switzerland, TASIS)
Popular events (Nuit de la Science 2016)
Events around the classroom (TecDays)
Outreach activities at SIB: where / who
Popular Events (public at large)
• Mystères de l’UNIL
• Nuit de la Science*
• Planète Santé Live*
• Expanding your horizons*
• Special events (open doors, Nuit des Musées, Diabetes day/JPOD, SCNAT200, café scientifique, etc.)
Mainly in Suisse Romande….
Nuit des Musées, Geneva, May 2017
* every 2 years
Planète Santé Live 2016
Outreach activities at SIB: where / who
Events around the classroom (12-18)
o Public outreach laboratories:
o ScienScope: Chimiscope + Bioscope (UNIGE), o L’Eprouvette (UNIL)
o (R)amène ta Science (UNIGE)
o Swiss Academy of Engineering Sciences SATW (TecDays)
o Swiss Chemical Society
Chimiscope, UNIGE
Outreach activities at SIB
In 2017
~2,100 participants in more than 65 sessions/events
Drug Design UniProt* Other** Total
1100 540 470 2110
TecDays (SATW) Nuit des musées Mystères de l’UNIL
Open Geneva Hackathon
+ Outdoor exhibition ‘Images de Science’ (MHS, Geneva, 2017-2018) + RTS 12h45
* Metagenomics (Blast@UniProt); see later
** Genome and genetic disease (BLAT)
Many thanks to all the people involved
Diana, Patricia, Vivienne
Andrea, Béatrice, Cristina, Damien, Emmanuel, Guilaine, Isabelle, Lionel, Michel, Nadine, Nevila, Patrick, Sylvain, Ursula
Aitana, Alexandra, Amel, Antoine, Camille, Davide, Frank, Frédéric, Frédérique, Marcin, Oriane, Oksana, Roberto, Robin,Thibault, Valérie,
Vincent
Salvo and the IT team for their help !
Outreach activities at SIB
Outreach activities at SIB:
o What
o Where / Who
o Outreach ‘Uniprot’
o Funding o Next events
Drug Design workshop
Menu
Outreach ‘UniProt’: 2017
Who: Public at large (150) Young students (390)
University - bachelor (219) University - master (110) Training - post-grade (100)
Where: (R) amène Ta Science, Popular events, University What: Metagenomics (pizza, air, birthday cake), BLAST
Courses@University / Training@SIB / Training@other
In 2017
~ 540 participants (public at large / young students)
~ 429 participants (university / post-grade) Activities based on non-programmatic access
Enlarge Your Horizons 2017
Many thanks to all the people involved
14F001 Elements of Bioinformatics
Anulka, Christian, Damien, Elisabeth, Emmanuel, Lionel, Michael, Ursula
Outreach activities at SIB:
o What
o Where / Who
o Outreach ‘Uniprot’
o Funding o Next events
Drug Design workshop
Menu
Funding
ChromosomeWalk.ch (191’000 CHF) (Melissa Davies)
Loterie Romande, Fondation Leenaards, Swiss Foundation for Excellence and Talent in Biomedical Research, Crédit Agricole, Fiduciaire Saugy
DocKing - Bioinformatics on the lookout for medicines of today and tomorrow
FNS Agora (PI O. Michielin): 2014-2017 (183'733 CHF) Computer-Aided Drug Design in action
FNS Agora (PI V. Zoete): 2017-2020 (189'949 CHF)
Comprendre la médecine personnalisée. L’exemple de l’oncologie.
Foundation Leenaards (projet SantéPerso; PI Vincent Zoete)
Publication
Chimia, just accepted
Outreach activities at SIB:
o What
o Where / Who
o Outreach ‘Uniprot’
o Funding o Next events
Drug Design workshop
Menu
Next events (2018)
• Mystères de l’UNIL, Lausanne, May 31 & June 1, 2, 3
• ‘Vivre ensemble’
• Nuit de la Science, Geneva (CBG), July 7, 8
• ‘Tout un art’
• Planète Santé Live, Palexpo Geneva, October 4, 5, 6, 7
• SIB 20 (Daniel & Franziska)
Outreach activities at SIB:
o What
o Where / Who
o Outreach ‘Uniprot’
o Funding o Next events
Drug Design workshop
Menu
The team
o Vincent Zoete o Antoine Daina o Ute Roehring o Patricia Palagi o Vivienne Gerritsen
www.drug-design-workshop.ch www.atelier-drug-design.ch
a bit of theory…
What is a drug?
How does it work?
Where do the drug molecules come from?
How to select the best drug candidates with the help of bioinformatics?
Why doing a genetic test before a treatment?
What is a drug?
How does it work?
Where do the drug molecules come from?
How to select the best drug candidates with the help of bioinformatics?
Why doing a genetic test before a treatment?
1060 molecules (theory)
35 million molecules
2,000 ‘drugs’ (FDA approved)
Aspirin (500 mg):
1.65 x 1021 molecules
A drug is a small organic molecule (100 atomes)
What is a drug?
How does it work?
Where do the drug molecules come from?
How to select the best drug candidates with the help of bioinformatics?
Why doing a genetic test before a treatment?
Protein’s active site is altered (mutated)
there is too little of a protein
there is too much of a protein (activity)
3
Les protéines
http://cdn.rcsb.org/pdb101/learn/resources/how-do-drugs-work-poster-high-res.pdf
What is a drug?
How does it work?
Where do the drug molecules come from?
How to select the best drug candidates with the help of bioinformatics?
Why doing a genetic test before a treatment?
S: 48.9 %
S*: 18.4 % N: 5.5 %
NB: 0.7 % ND: 26.4 %
http://pubs.acs.org/doi/pdf/10.1021/acs.jnatprod.5b01055 (2016) Where do the drug molecules come from ?
Synthesis of a natural product i.e. vitamine C
Synthetic drug Synthetic drug
derived from a natural product i.e. aspirin
Natural product Botanical drug
© V. Zoete
SwissDock
SwissTarget prediction
SwissADME (absorbtion & toxicity) + ~100 others
1060 molecules (theory)
35 million molecules
2,000 ‘drugs’
© V. Zoete
What is a drug?
How does it work?
Where do the drug molecules come from?
How to select the best drug candidates with the help of bioinformatics?
Why doing a genetic test before a treatment?
Molecular screening: an alternative
With the help of bioinformatics - Computer-Aided Drug Design (CADD) – you can select molecules:
with the highest affinity for their target (‘Docking’ score)
which are as specific as possible for their target (SwissTarget prediction)
which have the potential of becoming a drug (i.e. to be taken
orally, for the patient′s comfort and compliance, + toxicity, +
access to the brain or not, + which cytochrome is targeted)
(SwissADME)
how to introduce
Computer-Aided Drug Design
in practical…
www.drug-design-workshop.ch www.atelier-durg-design.ch
Docking suited for youth
SwissADME suited for youth Deduction game
www.drug-design-workshop.ch www.atelier-durg-design.ch
COX workshop
Biological context
Prostaglandin G/H synthase 1 & 2 (COX1 & COX2)
COX1 is expressed constitutively and produces prostaglandins to fine-tune physiological
processes
COX2 is inducible and typically produces inflammatory prostaglandins that mediate
responses to physiological stresses such as infection and inflammation
www.drug-design-workshop.ch/cox.php
draw a new molecule or
‘improve’ an existing molecule
Docking & Score:
Tens of thousands of different geometries and positions of the ligand in the protein are evaluated
The most probable position is shown in 3D
An affinity score is provided
• Polar interactions (shape)
• Electrostatic interactions
• Interactions between metal and ions (interaction π)
© V. Zoete
The most probable position is shown in 3D
An affinity score is provided
Cross-links to SwissTarget prediction and Swiss ADME
SwissTargetPrediction
‘similar molecules are prone to exhibiting similar biological activities’
SwissTarget Prediction compares your molecules (at the 2D and 3D structure levels) with 280,000 other molecules known to be active on 2,000 proteins.
Fingerprint based similarity
Fingerprint based similarity
www.SwissADME.ch
Predict important properties of the molecule in order to evaluate its potential of
becoming a drug to be taken orally
Absorption, Distribution, Metabolism, Excretion
Toxicity
http://education.expasy.org/cours/Outreach/SCS2016/SwissADME_Output_explanation.pdf
PMID:27218427
www.SwissADME.ch & BOILED-Egg
Optimization path of BCR ABL inhibitors leading to the oral anticancer drug ‐
ponatinib (in blue) and optimization path of AMPA receptor modulators leading to a brain penetrant investigational drug under clinical evaluation (in pink).
Iterative process…..you may have to go back to the beginning
BRAF workshop
http://www.ncbi.nlm.nih.gov/nuccore/568815591?report=fasta
chromosome 7 DNA sequence (GenBank database; 159’345’973 bp)
BRAF gene
A genetiT -> A c variation found in~
60 % of tcells he melanoma
Video: transition BRAF inactive -> BRAF active (V600E)
Control cell division The mutation in the BRAF gene ( V600E )
leads to a change in the shape of B-Raf protein
-> leads to the constitutive activation of downstream signaling in the MAP kinase pathway.
Control cell division
http://www.skincancer.org/publications/the-melanoma-letter/fall-2011-vol-29-no-2/how-zelboraf-extends-life-for-patients-with- metastatic-melanoma
www.drug-design-workshop.ch/braf.php
What is a drug?
How does it work?
Where does the drug come from?
How to select the best drug candidates with the help of bioinformatics?
Why doing a genetic test before a treatment?
Inhibitors that are specific for the V600E B-raf mutant have been recently introduced for treating late-stage melanoma Vemurafenib (Zelboraf®) is an example of a specific inhibitor of V600E B-Raf
Vemurafenib has been shown to dangerously favor tumor growth when the melanoma cells do not carry the B-Raf V600E mutation
Doctor prescriptions are only allowed after having sequenced the BRAF gene of the patient cancer cells, using the FDA-
approved cobas® 4800 BRAF V600 Mutation Test, to
ascertain sequence alteration.
Personalised medecine adapted for the for smaller users
IDO1 workshop
• When IDO1 is expressed in large quantities, tumours are able to evade the natural immune defense system.
• High expression of IDO1 stops immune cells (T lymphocytes) from proliferating.
• Certain side products which result from tryptophane degradation are toxic for T lymphocytes.
AMG-1, an imidazothiazole developed by Dainippon Sunimoto Pharma.
MMG-0358, a triazole designed by the SIB Swiss Institute of Bioinformatics. MMG-0358 has a strong affinity for IDO1 and is active in vivo.
PIM, an imidazole. PIM is one of the first inhibitors whose 3D structure complexed with IDO1 has been characterized. PIM has a weak affinity for IDO1 and is not very specific.
L1MT, or L-1-methyltryptophane, an inert analog of tryptophane that inhibits IDO1. L1MT is undergoing clinical tests for the treatment of breast and prostate cancer.
NLG-919, an imidazole developed by NewLink Genetics. NLG-919 is under clinical evaluation to treat solid tumors.
Many thanks to you !
Rechercher le nom latin de l’espèce sur Google (image)
