Hywel Williams

👋We are hiring a computational PhD student, interested in functional genomics and the non-coding genome. To continue developing our BRAIN-MAGNET algorithm recently published in Cell (cell.com/cell/fulltext/…). See vacancy for details! werkenbijerasmusmc.nl/en/vacancy/126…

@DrSamuelBHume Another modern miracle in our lifetime

Good luck @alex_tonks and @OwenHughes42 at the #ASH2025 conference. Safe journey & make sure you take your suncream (I’m not jealous at all) 😎

Amazing story about the power of a new gene-therapy treatment to help a little boy with the rare disease Hunter syndrome. Still early days in this field but it feels like this will become common practise in the not too distant future? bbc.co.uk/news/articles/…

Really looking forward to today’s @GenomicsEngland conference on long-read sequencing & how it’s driving research through to clinical impact. A fantastic line up of speakers, including the mighty @generoom Great to see representation from @cardiffuni too.

Finally got around to reading the "Ballistic Microscopy" paper, and it is really incredible. The paper opens with a compelling idea; one I hadn’t explicitly thought about before: “Light and electron microscopy utilizes interactions of either photons or electrons with matter to create images…” In other words, we see small objects by literally hurling things at them. Particles bounce off the object and reflect back into a lens, or scatter into a detector, which we then use to "see." The question asked in this paper, then, is thus: Can we hurl even larger things at cells to image them? The answer is yes. The gist of ballistic microscopy is that you first "bombard living cells with millions of nanoparticles traveling at ~1000 m/s." Each particle rips through the cell, picks up a tiny amount of cytoplasm, and comes out the other side. If you place a hydrogel film underneath the sample, the nanoparticles will crash into it and get stuck there; just like shooting a bullet into a ballistics dummy. Finally, you take out these nanoparticles and study the molecules they carry, like by using mass spectrometry or really anything else. This method preserves spatial information. The "nano-bullets" rip through the cell in a straight line, meaning that the pattern in the hydrogel corresponds with the nano-bullet's path through the cell. Nano-bullets embedded in the left side of the hydrogel will be carrying proteins, metabolites, and other "pieces" from the same side of the cell. So TL;DR, you're getting SPATIAL and MOLECULAR information, without having to label cells with anything. "This is akin to a 'physical image' being captures on a hydrogel 'film'," the authors write, "with physical material captured on these nano-bullets." Each bullet is between 50 to 1,000 nanometers in diameter. This is small but not exceptionally small. A typical E. coli bacterium measures about 2 micrometers long and 1 micrometer wide. Human cells are quite a bit larger. The next step will be to increase the resolution of this method, perhaps by using smaller nanoparticles. But then there is a tradeoff; if the nanoparticles are TOO small, they need to be accelerated at much higher speeds or they won't penetrate cleanly, or their path of travel will get deflected and mess up the spatial information. This first paper is just a proof-of-concept, of course. It reminds me a bit of Expansion Microscopy, at least in the narrow sense that it's a super creative, original solution to solving a problem. In expansion microscopy, you use a swellable polymer gel to physically ENLARGE a biospecimen, rather than try to make a microscope that can see smaller objects. It's an inverse solution to the microscopy resolution problem. In the original expansion microscopy paper (from 2015), samples were only expanded ~4.5x in each dimension. More recent papers have upped this to ~20x in each dimension; a huge improvement. I expect similar improvements for ballistic microscopy.

If you're doing any form of research related to rare diseases in Wales this is a must-join network. We need to work together to make us more than the sum of our parts, that way we can do real life-changing research and lead the way.

This is a fascinating read about what's lurking in our genome. A message from the dark genome @TheCrick crick.ac.uk/news/2025-10-0…

This is a must go conference for anyone working in the #Raredisease field in Wales 🏴󠁧󠁢󠁷󠁬󠁳󠁿 Come & see the breadth of research being done here & find like-minded people to network with.

25 years ago today, the first draft of the human genome was announced, a breakthrough that changed science forever 🧬 Read more about this achievement and the future of genomics over the next 25 years, here ⤵️ sanger.ac.uk/news_item/25-y…

@GeorgeKirov1 @Joshua_RSmith @ProfRobHoward Great and important work @GeorgeKirov1 and team!

Our new paper: Analysis of the whole population of Wales showed that ECT doesn't increase risk for dementia and might reduce mortality in the long term. doi.org/10.1111/acps.7… @Joshua_RSmith @ProfRobHoward

TOP STORY🗞️ A clinical-stage spinout company is launching with a $140 million (£107 million) investment – the most significant commercial investment into Welsh research to date. @cardiffuni spinout Draig Therapeutics will launch with the investment from leading international venture investors to advance the development of novel therapies for major neuropsychiatric disorders such as major depressive disorder. buff.ly/ZjXcFn5

Our book on ECT is out. People who had ECT or their relatives came together to share their journeys through severe depression and ECT. I was amazed by their stories. @DrAnnieHickox @ProfRobHoward @JunHongLi56447 @Joshua_RSmith @jonathanstea @JacquesSloman @DrT_Gergel

Finally, we show that there is a significant enrichment (9.5x10-9) of these pathogenic variants in patients with neurodevelopmental disorders. The reasons for this are unclear but suggests for such patients this would be a good first approach. Pls read and RT 4/4

It's important because pre-filtering genomic data to identify these variants is a rapid way to diagnose patients, leaving more time to analyse additional patients. If you don't have trio data don't worry, we show that 81% of variants in high CCRs are also pathogenic. 3/4

Really excited, exhausted and relieved to finally be able to share the results of my analysis of the @GenomicsEngland 100,000 Genomes Project dataset. Here's a link to free access to the manuscript: authors.elsevier.com/a/1l8iU3vlFV82… see below 🧵for main outcomes 1/4

A baby boy with a devastating genetic disease is thriving after becoming the first known person to receive a bespoke, CRISPR therapy-for-one, designed to correct his specific disease-causing mutation go.nature.com/4dkFKTV

Looking forward to my favourite #PublicEngagement event @pintofscience! I'll talk "how to train your virus" at @TinyRebelCdff on 20/05, discussing how we turned a disease causing "nasty" into a clinical stage anticancer medicine. Grab a pint, pop along! pintofscience.co.uk/event/from-ben…

Postdoc position #1 is live. Please apply / spread the word! lms.mrc.ac.uk/work/vacancies…