Project overview: Inhibition of HAO1 to treat primary hyperoxaluria type 1

Hello everybody! I am Sabrina, a third year DPhil student in Wyatt Yue’s lab at the SGC University of Oxford, co-supervised by Paul Brennan. I am fascinated by how a single base change in an enzyme-coding gene can lead to a diverse group of symptoms and how the severity of such diseases can be reduced Read More …

Presenting a poster at the annual Medical Sciences Division DPhil Day

Every summer my department holds a special mini-conference for the DPhil (aka PhD) students so that we can get to know each other and practice presenting our research. This year I took along a poster outlining my own project – Understanding the pathogenic mechanism of ACVR1 mutations in Diffuse Intrinsic Pontine Glioma – and presented Read More …

Purification of ACVR2, Alk3 (BMPR1A) and Alk6 (BMPR1B)

I had a couple of weeks off over August but I was back last week ready to crack on with work. As you’ve probably been following the ongoing saga, Ros and I have been struggling with expression of our key constructs. She had some good news on that on her latest post which has some Read More …

Virus titration and test expression of ACVR1 – some good news!

As I’ve mentioned in recent posts, our workhorse ACVR1 constructs have, for mysterious reasons, stopped expressing. This is clearly a massive problem, as with no protein we can not progress the project, and in the meantime, another DIPG patient has died, Aubreigh Nicholas, the 11-year-old girl who started the lemon face challenge. This is tragic, Read More …

Post-doc position available for a bioinformatician

Post-doctoral position for an ‘Omic-oriented’ parasitologist/bioinformatician in Montpellier University, France   Summary: –       Up to 3 years post-doc position in genomics and transcriptomics data analysis of the Plasmodium falciparum malaria parasite. –       In a young dynamic team based in Montpellier, South of France, with many worldwide collaborators –       Keywords: population genetics & genomics, single-cell RNA-seq, Read More …

Crystal structures of the CtUGGT double mutant S180C:T742C

The inter-domain conformational mobility of UGGT, the eukaryotic secretion glycoprotein folding checkpoint, is likely key to its ability of recognising and re-glucosylating a vast number of different misfolded glycoproteins, bearing N-linked glycan(s) at various different distances from the site(s) of misfold. Ongoing Molecular Dynamics simulations by Juan Blanco, Carlos Modenutti, and Marcelo Martí in Buenos Read More …

Analysis of NSD3 Isoform Expression from TCGA-LUSC Data

There are two major NSD3 isoforms expressed, long (aa 1-1437) and short (aa 1-645, differing in sequence from 620-645). The short isoform lacks a methyltransferase domain and, perhaps surprisingly, is the form attributed to NSD3’s role in acute myeloid leukemia (AML) [1]. I’ve previously used the TCGA-LUSC data-set [2] to test for differential expression based on the Read More …

Short form TGFBR1 (ALK5) purification and co-crystallisation with M4K2006 and M4K2089

In the absence of our “workhorse” protein, ACVR1 residues 208-499 (constitutively active Q207D mutant) (as we are still trying to work out why it won’t express at the moment), and the complete lack of crystals/diffracting crystals for the TGFBR1/FKBP12 complex, I have shifted to some other constructs we have to keep things moving. I had Read More …

Follow up to finding an antibody to detect EZH1 protein expression…the search continues

Following up on my previous post, I tested two antibodies I was planning on trying from Abcam and Novus that were used in previous publications. This time I tested directly in patient sample lysates and either saw no band, or many nonspecific bands (Figure 1). I have since reached out to the Orlando lab who Read More …

CaMKK2 Inhibitors: Building Diversity Around the Core Furopyridine Scaffold

Preparation of CaMKK2 analogs Pursuant to our aim of preparing a library of small molecule chemical probes around our most promising core scaffold, furopyridine, we sought to develop different chemistries that would allow us to achieve this objective. In the original synthetic route, 5-bromofuro[2,3-b]pyridine, 1, was able to undergo the Suzuki cross-coupling reaction to install Read More …