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   Update April 2019: If you are skilled and motivated, this position is still open! Drop me an email (see address at the bottom) Summary: –       Up to 3 years post-doc position in genomics and transcriptomics data analysis of the Plasmodium falciparum malaria parasite. –       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 …