Group Leader, University of Cambridge, Department of Pathology. Cancer Immunology. Immunogenomics. Somatic evolution. machado-lab.org
Cambridge, England
- Tweets 111
- Following 239
- Followers 745
- Likes 218
PhD and Postdoc positions available! Interested in how our immune system evolves with a growing tumour, and how we can use that to fight cancer? Love data analysis? Applications now being accepted in the Machado Lab (machado-lab.org/contact) at the University of Cambridge.
7
154
457
74,678
So proud of this new study. We developed naive and memory B and T single-cell expansion protocols and produced lymphocyte and blood stem cell genomes, from healthy individuals aged 0-81. I am still stunned at the biological insights revealed. [1/10]
biorxiv.org/content/10.1101/…
6
95
337
I’m thrilled to shared that this August I’ll join the Department of Pathology of the University of Cambridge @Cambridge_Uni as a Group Leader. The Machado Lab will study the somatic evolution of the adaptive immune system to understand aging and disease.
17
16
221
29,408
How much selection is there on synonymous sites? And which processes are responsible? We find that ~15% of synonymous sites in preferred codons are under strong purifying selection. Splicing is the runner up! genetics.org/content/early/2…
1
28
120
Just out in @eLife, we find evidence of parallel seasonal adaptation across 20 Drosophila spring/fall population samples collected in North America and Europe. elifesciences.org/articles/6…
2
41
92
Join us! The Machado Lab at @Cambridge_Uni is looking for an enthusiastic RA to be a core member of the team and lead the lab's data generation efforts, seeking to understand how tumour and immune cells co-evolve and contribute to cancer progression. jobs.cam.ac.uk/job/47922/
37
62
16,701
Our newest paper, just out on bioRxiv! Strong purifying selection on codon bias- accounts for most strong selection on synonymous sites.
Strong purifying selection on codon usage bias biorxiv.org/cgi/content/shor… #bioRxiv
29
49
This was a close collaboration with Peter Campbell and @scienceadvocacy and other great contributors including @gaddyg @KirstenKubler @PolakPaz @KSaebParsy EmilyMitchell @ninaoebro @imartincorena @FrancescoMaura4 @ATJCagan @d4l997 @MathijsSanders. [10/10]
1
18
Similar mutational profiles but increased structural variation rate in cancer compared with normal lymphocytes suggests that malignant transformation is associated with the emergence of cancer-specific genomic instability. [9/10]
1
16
Our results suggest that fluctuating selection is an important evolutionary force in Drosophila. This study is a community effort, with samples from 19 different labs @DrosRTEC, wrapped up by brilliant collaborators @BerglandAlan @paulrschmidt @PetrovADmitri
2
4
10
New study that elegantly addresses somatic mutation rate vs lifespan. Insta-classic. Congrats @ATJCagan @imartincorena
I am incredibly excited to share our preprint ‘Somatic mutation rates scale with lifespan across mammals’In this paper we provide an unprecedented description of somatic mutation across mammals.
biorxiv.org/content/10.1101/…
An illustrated tweetorial…[1/17]
1
1
10
Please join us for an afternoon of talks on Nov 30th at the second annual Somatic Evolution and Tumour Microenvironment Symposium, #SETM2020! crick.zoom.us/webinar/regist…
3
9
Structural variation was 16-fold higher in lymphocytes than stem cells, with ~15% of deletions being attributable to off-target RAG activity. [8/10]
1
10
This is a transformative sequencing method. I’m thrilled to have been involved in its development!
Excited to share our latest work. We present NanoSeq, a new duplex sequencing method with <5 errors per billion sites in single DNA molecules. A leap in our ability to study mutation in any tissue. 1/ nature.com/articles/s41586-0…
1
8
We are able to time mutational processes by associating mutation location with cell-type-specific chromatin marks. Confirms that both naive and memory T cells diverged early from stem cells and that SBS9 occurs in the germinal center. [7/10]
1
9
Seasonally fluctuating polymorphisms are found throughout the genome, but are particularly enriched in large chromosomal inversions. 2/5
1
2
8
Elegant study leveraging longitudinal blood sampling pre-AML diagnosis (up to 15 years prior!) to quantitatively describe blood cancer evolution.
How do healthy tissues evolve to become cancerous? Delighted to share our latest research tracking the somatic evolution that occurs in the decades before AML. 👇Implications for early detection and early interception. biorxiv.org/cgi/content/shor…
7
2,080
Yes! Would love feedback so find me at poster 765C @ #DROS17
Come see the newest on genomics of seasonal adaptation across multiple pops of D. melanogaster. Poster by @heatherEmachado 765C #DROS17
1
3
6
We find broad concordance between seasonal (spring to fall) and latitudinal (high to low latitude) frequency change, suggesting that the environmental factors that drive these patterns must both shift between seasons locally and vary spatially from south to north. 3/5
1
1
5
The direction of allele frequency change at seasonally variable polymorphisms can be predicted by weather conditions in the weeks prior to sampling (min temp in fall and max temp in spring), linking the environment and the genomic response to selection. 4/5
1
1
5
Memory T cells bear marks of exogenous mutational processes. E.g. cells with signature 7, associated with UV damage, can have 1000’s of these mutations, and have shorter telomeres indicating turnover in these putative skin-resident lymphocytes. [4/10]
2
1
5
Should be a quality SETM afternoon! Or morning in the US, or night in the East, …. But please join us wherever you are- it’s virtual and free!
Happy to announce the Somatic Evolution and Tumour Microenvironment (Virtual) Symposium 2021! #SETM2021
Only a month from now, half a day of cool scientific talks; register for free here:
crick.zoom.us/webinar/regist…
1
5
Strong association of SBS9 with late-replication timing contributes to a new hypothesized model where SBS9 arises from polymerase-eta bypass of background DNA lesions induced by the high levels of replicative and oxidative stress experienced by germinal center B cells. [6/10]
1
6
High mutation burden in memory B cells is driven by SBS9. We show SBS9 is correlated with telomere lengthening and somatic hypermutation. Memory B cells acquired ~18 of these “off-target” mutations for every one on-target IGV mutation during the germinal center reaction. [5/10]
1
5
What a great meeting #EMBLCanGen! Thank you @ATJCagan for the beautiful summary.
Heather Machado on the life history of normal human lymphocytes revealed by somatic mutations #EMBLCanGen
3
Useful cheat-sheet of human pop gen numbers!
Sharing this in case it's useful: I find that students often have a hard time conceptualizing quantitative parameters in genomics and popgen
Here's a cheat-sheet I put together for teaching. It's also part of a textbook I have been writing on human genetics (more on that below)
1
3
1,226
All lymphocyte subsets had higher mutation burdens than stem cells. The rate of accumulation in T cells (SNVs/year) was higher than B and stem cells, consistent with early T cell divergence from stem cells and mutation accumulation in different states/environments. [3/10]
1
3
A pleasure and honour to work with the talented @dlawrie42 and @PetrovADmitri
1
2
Great study with fundamental insight into mutation acquisition
How many mutations would we acquire if there was no mismatch repair?
Excited to share our latest work. Read all about how mutation patterns and rates are shaped by mismatch repair deficiency (MMRD) genotype, tissue type and malignant transformation.
biorxiv.org/content/10.1101/…
1
2
Accelerating Wright-Fisher Forward Simulations on the Graphics Processing Unit biorxiv.org/content/early/20…
2
The mutational landscape of normal lymphocytes chronicles off-target effects of immunological diversification and the consequences of differentiation, proliferation and residency in diverse microenvironments. [2/10]
1
2
Congrats on the recognition of your great work! @SerenaNikZainal
1
I’m case you’re feeling down about the speed of your career progression, now you know you’re in good company.
Age at first R01 grant... just when you think it can't keep getting more ridiculous it does. Median age is now up to 42... long live the long lived gerontocracy. We desperately need to do more to accelerate the careers of younger scientists in the US tinyurl.com/2utfbj2m
1
Beautiful somatic evolution study, kicking off #SETM2020
1