Laura De Conti,
Hyung Chul Kim,
Narjes Rohani,
@chundru.bsky.social
Laura Watts,
@ruebenadawes.bsky.social
@yuyangchen.bsky.social
@alextremophile.bsky.social
Michael Griffiths,
Sam Scott,
Rosemary Bamford,
Jonathan Mill,
@carolinefwright.bsky.social
Marco Baralle,
@stephansanders.bsky.social
Thank you *very much* to my co-authors, supervisors, and funders for your contributions, belief and support 🙏
@wellcometrust.bsky.social
@ndm.ox.ac.uk
@idrm.ox.ac.uk
@icgeb.bsky.social
@nickywhiffin.bsky.social
We also increased expression of a 5th gene by excluding additional uORFs downstream of the ‘skippable’ exon - highlighting the importance of redundancy between these features ⚠️ But, we also show uORFs can also work additively, such that you get an incremental boost each time you remove one! 💡
We investigated 6 genes in the lab associated with NDD 🧠. Using a luciferase assay, we found the expression of 4/6 genes increased by excluding a uORF-containing exon! 📈 Laying the groundwork for SSO investigations 🔎
Outcome?
We wrote a pipeline to identify genes:
1. associated with conditions caused by loss of function in one allele,
2. with uORFs,
3. which could be removed by skipping out a 5'UTR exon (using an RNA therapeutic which alters splicing or CRISPR).
✨ And found >50! ✨
How?
By excluding repressive features, uORFs, from mRNA.
uORFs make ribosomes begin translation early in the 5’UTR 🏃➡️🟢——>🛑
Afterwards, ribosomes need some distance to reset 😴, and might leave 🙅, This leads to lower translation of the main coding sequence.
Most approaches to increase gene expression are contextually unique, but this method can be applied to multiple genes! 🙌
Why?
People (like me!) can have genetic conditions because one of their two copies of a gene isn’t working.
🧬✅ 🧬✅ = 😊
🧬✅ 🧬❌ = 🙁
We look at a new way of boosting the output of the remaining functional copy.
🧬✅ ✅ 🧬❌ = 😊
*A new pre-print on increasing gene expression!* 🧬📈
doi.org/10.64898/202...
New paper on everyone’s favourite topic, QC!
We show why you should do genotype-level QC on your WGS data
www.biorxiv.org/content/10.1...
Very real quotes about this paper -
“The most exciting, mind-blowing paper of the year!”
“On a par with Fisher 1918”
“I read it every night. Just so beautiful”
Duncan is a great mentor! If you are interested in doing a PhD in genomics & stats see the link below for a great opportunity 👀
Enjoyed the Med Sci DTC symposium yesterday. It was great to share some of my work and catch up with other GMS students 🧬
Thank you @medsci.ox.ac.uk!
A few weeks ago, I had an incredibly emotional call with James Coney, a writer for the Sunday Times whose son Charlie was in the @genomicsengland.bsky.social 100k project and was recently diagnosed with ReNU syndrome. This beautiful article tells their story ❤️ www.thetimes.com/article/0bcc...
#january Day 7
Less than a month to go until this year’s CPM #ResearchShowcase, with a theme of #PersonalisedPrevention!
More details and sign up here, it’s going to be a great day:
I want to extend a huge thank you to the @nickywhiffin.bsky.social lab for having me this past month to work on various projects using the @GenomicsEngland data. I learned a ton during my time @ox.ac.uk and continue to drink tea at least 3 times per day. Cheers!
Excited to announce that my F99/K00 fellowship entitled, “A multi-omics approach to understanding pediatric epilepsies,” was officially funded today!
And a huge thank you to @hcmefford.bsky.social for being the greatest mentor ever and always supporting me in these endeavors 🧬🧠 Cheers!
HUGELY EXCITED to be a trainee 🌱 in the MRC CoRE for Therapeutic Genomics! 🧬
Most rare conditions have no effective treatment, together we will work to change this 🚀
www.ukri.org/news/mrc-lau...
Congratulations to @nickywhiffin.bsky.social on being awarded the Balfour Lecturer! Her innovative contributions on the role of genetic variants in rare diseases are shaping the future of research and discovery. We look forward to her inspiring lecture!
genetics.org.uk/medals-and-p...
📣 Big news! Our tag-team effort on common variants in rare neurodevelopmental conditions is now out in Nature 📣
Co-first authoring with the brilliant Qinqin Huang🌟—proof that teamwork does make the dream work. 💪 www.nature.com/articles/s41...
Picture of six people smiling in the snow in the city of Denver
A picture of Yuyang Chen giving a presentation. In the background a large screen has a slide saying "Variants in RNU4-2 cause a neurodevelopmental disorder (ReNU syndrome)". In the foreground, many people sit listening to the talk.
A poster is being presented while others listen.
Back home and reflecting on a fantastic week at #ASHG24.
It was wonderful to reconnect with friends, make new connections, and be surrounded by amazing science! 🧬
This was my first time attending ASHG with many of my amazing team (see below). They did an incredible job representing the group 🥰 1/2
