Welcome to the Weatheritt lab website

We use computational approaches and molecular biology to investigate how post-transcriptional processes, and in particular alternative splicing, regulate protein function in the nervous system. Our goal is to uncover the root causes of neurodevelopmental disorders, such as autism spectrum disorder, and develop novel therapeutic interventions.

News

- 2020/05 PostDoc position in RNA biology available, preference for those with imaging experience. Apply Now!!
- 2020/05 Paper published in Nature as part of the HURI consortium.
- 2020/02 Robert published a Molecular Cell paper with Blencowe lab.
- 2019/10 Welcome Grazi, Peter and Otto!
- 2019/07 Paper published in Genome Biology. We uncover mechanisms controlling exonisation, which permit the emergence of lineage-specific regulation.
- 2019/07 Congratulations Javier on receiving the Ramon Areces Foundation Postdoctoral Fellowship!
- 2019/07 Congratulations Gaby on receiving UIPA PhD fellowship!
- 2019/05 Congratulations Juli on receiving UIPA PhD fellowship!
- 2019/03 Welcome Juli!
- 2019/01 Paper published in Nature Review Genetics. Always a pleasure collaborating with Ben, Mathieu and Sabine.
Autism spectrum disorder: insights into convergent mechanisms from transcriptomics.
- 2018/12 Weatheritt lab has doubled in size (again)! Welcome Javi and Gaby!
- 2018/07 Paper just published in Molecular Cell. Great working with Ben and Tim
Efficient and accurate quantitative profiling of alternative splicing patterns of any complexity on a laptop
- 2018/06 Weatheritt lab is a physical entity!!

Research

Lineage-specific alternative splicing and neuronal complexity
Human have approximately 86 trillion neurons. C. elegans has exactly 302 neurons. Humans and C. elegans have approximately the same number of genes. How is this complexity encoded? We are interested in investigating how
Relevant Publications:
Gueroussov, Weatheritt et al. Cell 2017
Irimia et al. Cell 2014
Reyes et al. PNAS 2013
Genetic variation and post-transcriptional control
Can the flexibility of alternative splicing also be its undoing? Could the evolutionary advantage of AS in creating phenotypic diversity also allow it create aberrant phenotypes that result in disease?

Relevant Publications:
Avgan et al. Genome Biology. 2019
Sterne-Weiler, Weatheritt et al. Molecular Cell 2018:
Weatheritt and Babu. Science 2013:
Alternative splicing and single molecule microscopy
We use single molecule approaches to understand functional differences between alternative proteins . Collaboration with Senthil Arumugam's Lab (his image) and UNSW Single Molecule Science centre
Relevant Publications:
Irimia et al. Cell 2014
York et al. bioRxiv
Alternative splicing and
the proteome
We previously demonstrated that tissue-specific alternative splicing rewires proteomic networks by targeting linear motifs within intrinsically disorder regions. How dynamic is this process? Is it regulated by cell signalling?
Relevant Publications:
Luck et al. Nature 2020
Weatheritt and Gibson. TIBS. 2012
Weatheritt et al. NSMB. 2016

Recent Publications

Splicing and Evolution: how to create new exons
We identified a exonisation is controlled by a multilayered mechanism that modulates the "window of opportunity" for cryptic exon recognition.

Avgan et al.
Genome Biology (2019)
Small but mighty: microexons and autism

We identify a highly conserved and brain-specific set of alternatively spliced microexons. These microexons modulate protein-protein interactions of primarily synaptic proteins and are frequently misregulated in the brain of autistic individuals.

Irimia et al. Cell (2014)

Expanding our view of transcriptome complexity
We've created a light-weight, lightening fast method for the quantitative profiling of AS from raw RNA-seq reads at the event-level (Whippet.jl). We identify >30% of human genome under complex splicing events and cancer genomes show more highly complex transcriptomes.

Sterne-Weiler, Weatheritt et al.
Molecular Cell (2018)
Why translate locally?

Why are certain mRNA transported to a distal location and translated on-site? In this paper, our findings suggest that the asymmetric protein distribution by mRNA localization enhances interaction fidelity and signaling sensitivity by ensuring highly promisicious proteins are only translated at the right place at the right time.

Weatheritt et al. NSMB (2014)

Splicing and Evolution: how to create new phenotypes
We identified a series of mammalian-specific alternative splicing events that regulate higher order protein assemblies. This mechanism expands the regulatory complexity of mammalian transcriptomes and proteomes.

Gueroussov, Weatheritt et al.
Cell (2017)
The hidden codes that shape protein evolution

We purpose that in certain protein coding genes codon preference is highly restricted by other "regulatory" codes that govern regulation in the genome and transcriptome.

Weatheritt & Babu Science (2013)

Full List of Publications

By Journal: Cell (2), Science (1), Nature (1), Chemical Reviews (2), Nat Struc Biol (2), Mol Cell (3), PNAS (1), E-life (1), Science Signal (1), TIBS (1), Protein Sci (1), Mol BioSyst (2), Curr Opin Stru (1), NAR (5), Bioinfomatics (1), Front Neuro (1), Hum Brain Mapp (1), Nature Review Genetics (1), Genome Biology (1)
By year: 2020 (1), 2019 (2), 2018 (1), 2017 (2), 2016 (3), 2015 (1), 2014 (7), 2013 (4), 2012 (5), < 2012 (3)


- Alternative splicing: regulation, biological significance and evolution
1) Luck K, Kim DK, Lambourne L, Spirohn K,..., Weatheritt RJ and HURI Consortium. Nature. 2020 Apr;580(7803):402-408A reference map of the human binary protein interactome.
2) Rodrigues DC, Mufteev M, Weatheritt RJ, Djuric U, Ha KCH, Ross PJ, Wei W, Piekna A, Sartori MA, Byres L, Mok RSF, Zaslavsky K, Pasceri P, Diamandis P, Morris Q, Blencowe BJ, Ellis J. Shifts in Ribosome Engagement Impact Key Gene Sets in Neurodevelopment and Ubiquitination in Rett Syndrome. Cell Reports. 2020 Mar 24;30(12):4179-4196
3) Gonatopoulos-Pournatzis T, Niibori R, Salter EW, Weatheritt RJ, Tsang B, Farhangmehr S, Liang X, Braunschweig U, Roth J, Zhang S, Henderson T, Sharma E, Quesnel-Vallières M, Permanyer J, Maier S, Georgiou J, Irimia M, Sonenberg N, Forman-Kay JD, Gingras AC, Collingridge GL, Woodin MA, Cordes SP, Blencowe BJ. Autism-Misregulated eIF4G Microexons Control Synaptic Translation and Higher Order Cognitive Functions. Molecular Cell. 2020 Jan 25. pii: S1097-2765(20)30006-X.
4) Avgan N, Wang JI, Fernandez-Chamorro J, Weatheritt RJ. Multilayered control of exon acquisition permits the emergence of novel forms of regulatory control. Genome Biology. 2019 Jul 17;20(1):141
5) Quesnel-Vallières M, Weatheritt RJ, Cordes SP, Blencowe BJ. Autism spectrum disorder: insights into convergent mechanisms from transcriptomics Nat Rev Genetics. 2019 Jan;20(1):51-63
- on cover!
6) Sterne-Weiler T*, Weatheritt RJ*, Best A, Ha KCH, Blencowe BJ. Whippet: an ultra fast and accurate alignment and quantification of RNA-seq data for analysis of alternative splicing. Molecular Cell 2018 Oct 4;72(1):187-200.e6
7) Gueroussov S*, Weatheritt RJ*, Sterne-Weiler T, O’Hanlon D, Lin ZY, Gingras AC, Blencowe BJ§. Mammalian-specific regulation of higher-order hnRNP protein assemblies controls alternative splicing. Cell 2017 Jul 13;170(2):324-339.e23.
- research highlighted by Nature Review Molecular Cell Biology
8) Han H, Braunschweig U, Gonatopoulos-Pournatzis T, Weatheritt RJ, Hirsch CL, Ha KCH, Radovani E, Nabell-Shah S, Sterne-Weiler T, Wang J, O’Hanlon D, Pan Q, Ray D, Vizeacoumar F, Datti A, Magomedova L, Cummins CL, Hughes TR, Greenblatt JF, Wrana JL, Moffat J, Blencowe BJ. Multilayered control of alternative splicing regulatory networks by transcription factors. Molecular Cell. 2017 Feb 2;65(3):539-553.e7.
9) Weatheritt RJ, Sterne-Weiler T, Blencowe BJ. (2016) The ribosome-engaged landscape of alternative splicing. Nat Struct Mol Biol. 2016 Dec;23(12):1117-1123
10) Dominguez D, Tsai YH, Weatheritt R, Wang Y, Blencowe BJ, Wang Z. (2016) An extensive program of periodic alternative splicing linked to cell cycle progression. E-life. 2016 Mar 25;5
11) Irimia M, Weatheritt RJ, Ellis JD, Parikshak NN, Gonatopoulos-Pournatzis T,Babor M, Quesnel-Vallières M, Tapial J, Raj B, O'Hanlon D, Barrios-Rodiles M, Sternberg MJ, Cordes SP, Roth FP, Wrana JL, Geschwind DH, Blencowe BJ. (2014) A highly conserved program of neuronal microexons is misregulatedin autistic brains. Cell. 159(7):1511-23
- perspective in Cell by Yang and Chen, and in EMBO Journal by Darnell. Research highlighted by Nature Review Neuroscience and Faculty of 1000
12) Reyes A, Anders S, Weatheritt RJ, Gibson T.J, Steinmetz L, Huber W. (2013) Drift and conservation of differential exon usage across tissues in primate species. PNAS. 110(38)
13) Weatheritt RJ, Davey NE, Gibson TJ. (2012) Linear motifs confer functional diversity onto splice variants. Nucleic Acids Res 40, 7123-7131
- recommended reading by Nature Review Genetics
14) Weatheritt RJ and Gibson,TJ. (2012) Linear Motifs: Lost in (Pre)Translation Trends Biochem Sci i 37, 333-341 [Review article]

- Genomic and post-transcriptional regulation
15) Latysheva NS, Oates ME, Maddox L, Flock T, Gough J, Buljan M, Weatheritt RJ, Babu MM. (2016) Molecular Principles of Gene Fusion Mediated Rewiring of Protein Interaction Networks in Cancer. Molecular Cell. 2016 Aug 18;63(4):579-92
16) Weatheritt RJ, Gibson TJ, Babu MM. (2014) Asymmetric mRNA localization contributes to fidelity and sensitivity of spatially localized systems. Nat Struct Mol Biol. 21(9); 833-9
- research highlighted by Faculty of 1000 and by Nature.com
17) Weatheritt RJ, Babu MM. (2013) Evolution. The hidden codes that shape protein evolution. Science 342(6164)

- Intrinsically disordered regions and short linear motifs (SLiMs)
18) Latysheva NS, Flock T, Weatheritt RJ, Chavali S, Babu MM. (2015) How do disordered regions achieve comparable functions to structured domains? Protein Sci. 2015 Jun;24(6):909-22 [Review article]
19) Uyar B, Weatheritt RJ, Dinkel H, Davey NE, Gibson TJ. (2014) Proteome-wide analysis of human disease mutations in short linear motifs: neglected players in cancer? Mol BioSyst; 10(10): 2626-42
20) Van Roey K, Uyar, Weatheritt RJ, Dinkel H, Seiler M, Budd A, Gibson TJ, Davey NE. (2014) Short linear motifs: ubiquitous and functionally diverse protein interaction modules directing cell regulation. Chemical Reviews. 114(13):6733-78 [Review article]
21) Van der Lee R, Buljan M*, Lang B*, Weatheritt RJ*, Daughdrill GW, Dunker AK, Fuxreiter M, Gough J, Gsponer J, Jones DT, Kim PM, Kriwacki RW, Oldfield CJ, Pappu RV, Tompa P, Uversky VN, Wright PE, Babu MM. (2014) Classification of Intrinsically Disordered Regions and Proteins. Chemical Reviews 114 (13): 6589-631 [Review article]
22) Flock T*, Weatheritt RJ*, Latsheva NS, Babu MM§. (2014) Controlling entropy to tune the functions of intrinsically disordered regions. Curr Opin Struct Biol. 2014 Jun;26C:62-7 [Review article]
23) Dinkel H, Van Roey K, Michael S, Davey NE, Weatheritt RJ, Born D, Speck T, Krüger D, Grebnev G, Kuban M, Strumillo M, Uyar B, Budd A, Altenberg B, Seiler M, Chemes LB, Glavina J, Sánchez IE, Diella F, Gibson TJ. (2014) The eukaryotic linear motif resource ELM: 10 years and counting. Nucleic Acids Res D259-66
24) Van Roey K, Dinkel H*, Weatheritt, RJ*, Gibson TJ, Davey NE. (2013) The switches.ELM resource: a compendium of conditional regulatory interfaces within the intrinsically disordered proteome. Science Signaling. 6(269): rs7
25) Weatheritt RJ, Jehl P, Dinkel H, Gibson TJ. (2012) iELM – a web server to explore short linear motif mediated interactions Nucleic Acids Res. doi: 40, W364-9
26) Weatheritt RJ, Luck K, Petsalaki E, Davey NE, Gibson TJ. (2012) The identification of short linear motif mediated interfaces within the human interactome Bioinformatics 28(7):976-982
27) Davey NE, Van Roey K*, Weatheritt RJ*, Toedt G, Uyar B, Altenberg B, Budd A, Diella F, Dinkel H, Gibson TJ. (2012) Attributes of short linear motifs. Mol Biosyst 8, 268-281.
28) Dinkel H, Michael S, Weatheritt RJ, Davey NE, Van Roey K, Altenberg B, Toedt G, Uyar B, Seiler M, Budd A, Jodicke L, Dammert MA, Schroeter C, Hammer M, Schmidt T, Jehl P, McGuigan C, Dymecka M, Chica C, Luck K, Via A, Chatr-Aryamontri A, Haslam N, Grebnev G, Edwards RJ, Steinmetz MO, Meiselbach H, Diella F, Gibson TJ. (2012) ELM--the database of eukaryotic linear motifs. Nucleic Acids Res 40, D242-D251.
29) Gould CM, Diella F, Via A, Puntervoll P, Gemund C, Chabanis-Davidson S, Michael S, Sayadi A, Bryne JC, Chica C, Seiler M, Davey NE, Haslam N, Weatheritt RJ, Budd A, Hughes T, Pas J, Rychlewski L, Trave G, Aasland R, Helmer-Citterich M, Linding R, Gibson TJ. (2010) ELM: the status of the 2010 eukaryotic linear motif resource. Nucleic Acids Res 38, D167-80.

- Neuroscience
30) Yanashima R, Kitagawa N, Matsubara Y, Weatheritt R, Oka K, Kikuchi S, Tomita M, Ishizaki S. (2009) Network Features and Pathway Analyses of a Signal Transduction Cascade. Front Neuroinform 3, 13.
31) Krumbholz K, Nobis EA, Weatheritt RJ, Fink GR. (2009) Executive control of spatial attention shifts in the auditory compared to the visual modality. Hum Brain Mapp 30, 1457-146

People

Robert Weatheritt
EMBL Australia Group Leader
Education: University of York (MRes), EMBL Heidelberg (PhD), MRC Laboratory of Molecular Biology and Donnelly Centre (PostDoc)
Hometown: London, England
Other activities: Diving, Sailing, Squash
Doing things that PIs do
60%
Experiments
30%
Admin
20%
Gabriela Rodriguez
PhD Student
Education: National Autonomous University of Mexico (BSc), CINVESTAV (MSc)
Hometown: Mexico City, Mexico
Other activities: Baking, Tae Kwon Do, Yoga

Learning transcriptomics
60%
Experiments
40%
Finding best espresso in Sydney..
10%
Javier Fernandez-Chamorro
Postdoctoral Fellow
Education: Autonomous University of Madrid (MSc), Centre of Molecular Biology Severo Ochoa (CSIC-UAM) (PhD)
Hometown: Madrid, Spain
Other activities: Climbing, Hiking and cooking

Setting up the lab
30%
Experiments
70%
Finding equipment...
10%
Giulia Wang
PhD Student
Education: University of Toronto (BSc and MSc)
Hometown: Lausanne, Switzerland.
Other activities: Reading/writing music critiques

Exploring the beautiful world of RNA
80%
Discussions with inspiring colleagues
20%
Greeting deadly mates with 8 legs
10%
Grazi Vieira
Lab Manager
Education: Federal University of Ouro Preto (MSc), Federal University of Minas Gerais (PhD)
Hometown: Belo Horizonte/Minas Gerais - Brazil.
Other activities: Rock Climbing, Capoeira, Yoga, dancing Forró

Managing the Lab
50%
Exciting Experiments
50%
Appreciating every minute of life
100%
Peter Kjer Hansen
Student
Education: University of Copenhagen (BSc and MSc)
Hometown: Copenhagen, Denmark.
Other activities: Exploring newer music history, reading actual books, and coffee

Experiments
70%
Searching for links between RNA and primary cilia
30%
Moving my belongings across Sydney
10%
Hei (Otto) Yuen
Year Aboard Student
Education: Imperial College, London
Hometown: Hong Kong, China.
Other activities: Drawing, Drumming, Wushu

Reading papers
40%
Learning from people in the lab
50%
Evading extradition to Dreamland
20%
You?
Postdoc or Graduate Student
Education:
Hometown:
Other activities:

Join us

Postdocs

If you are interested in our research and you have a recent PhD degree in molecular biology, proteomics/genomics, computation biology, neuroscience or bioinformatics, please send an email to Robert explaining your research interests (also include your CV and contact details of three references). We are always interested in motivated candidates. Potential candidates who are interested in joining us should be competitive to apply for external fellowships and sources of funding such as the ARC fellowship, NHMRC fellowship, Marie-Curie Fellowship or HFSP Fellowship.

Graduate students

If you are interested in joining the lab or doing a master's project, please send Robert an email (r.weatheritt@garvan.org.au) or come by his office. Also, have a look at the Garvan institute graduate programme or EMBL Australia Partnership PhD Program for information about the application process.

Undergraduate students

We may have openings for undergraduate students. If you are interested, please send Robert an email with a short explanation of your interests. Please attach your transcript and CV in the email. Also, have a look at the Garvan institute undergraduate programme for more information.

Contact

Email: r.weatheritt@garvan.org.au

Or visit us at the Garvan: