蘑菇视频下载安卓

Student discovers how mutations cause childhood neurological diseases

Mapping of a key brain enzyme reveals links to childhood disability and cancer 鈥 and could unlock new drug therapies
PhD researcher Jack Welland

A researcher at St John鈥檚 has discovered the molecular structure of a key enzyme in severe diseases that he hopes will lead to better treatments for young patients.

PhD student Jack Welland led a new study that found exactly what happens when an enzyme known as B4GALNT1 mutates, causing neurological disorders in children such as hereditary spastic paraplegia type 26 鈥 a condition characterised by progressive leg stiffness, spasms, and cognitive impairment.

鈥淥ur motivation was to better understand how these diseases work and why they are caused by these faulty proteins鈥, said Welland.

鈥淚f these proteins lose function, they cause serious damage to neurons 鈥 nerve cells that send messages all over your body 鈥 which leads to the loss of limb function and intellectual disability.

鈥淚mportantly, we were able to identify for the first time the molecular mechanisms for how some of these mutations cause life-limiting neurological diseases.鈥

The research, undertaken at the Cambridge Institute for Medical Research (CIMR) and the University of Warwick, has been published in the journal, Nature Communications.

Enzymes are proteins that act as biological catalysts, speeding up chemical reactions within living organisms.

B4GALNT1 is involved in the biosynthesis of complex brain gangliosides 鈥 crucial components of cell membranes that are important for normal brain function.

Imbalances in the metabolism of B4GALNT1 not only cause hereditary spastic paraplegia, but the enzyme is also over-expressed in some cancers, particularly neuroblastoma 鈥 the most common cancer in babies and young children that originates outside the brain.

鈥淭he cancer cells in neuroblastoma produce far more of specific gangliosides made by these enzymes than normal,鈥 said Welland, a third-year Michael House PhD Scholar in the Deane Lab at CIMR.

鈥淭hrough our research we mapped the molecular structure of the enzyme, and a potential strategy now is to design drugs that can inhibit these enzymes to alleviate the children鈥檚 symptoms.鈥

Atomic simulations of the newly solved B4GALNT1 structure show it burying into lipid membranes facilitating the sugar headgroup of a ganglioside lipid to enter in the enzyme's active site. Credit: Jack Welland

The researchers combined experimental and computational simulation strategies to investigate how B4GALNT1 functions. They found the enzymes have special loops they insert into cell membranes to draw themselves close to lipids, which make up the membranes.

The lipids with sugar groups joined to their heads are known as glycolipids, which organise themselves into two layers to shield everything within the cell. It is the glycolipids called gangliosides that the scientists studied to model the loss of protein function that causes neurological diseases.

"These particular lipids and lipid-synthesising enzymes are diverse biomolecules that have been considerably understudied at the molecular level before now,鈥 said Welland, whose ambition to go into research was inspired by his older sister Alicia, who has multiple sclerosis.

鈥淥ur research to identify the molecular structure of the enzyme paves the way not only for new drug therapies but also for helping to understand their role in a range of diseases 鈥 including neurological diseases, cancers and in autoimmune diseases such as lupus.鈥

Welland is now developing computational tools for researchers to quickly see how metabolism changes for the special lipids in different diseases.

Reference

Welland, JWJ, Barrow, HG, Stansfeld, PJ聽et al: 鈥楥onformational dynamics and membrane insertion mechanism of B4GALNT1 in ganglioside synthesis鈥. Nature Communications, July 2025.

News
Research

Related articles

The Rev'd Graham Dunn, Chaplain of St John's College, blesses the punt bearing the name Louis Leakey while 蘑菇视频下载安卓 try it out
Cambridge punt blessed by Chaplain and launched onto River Cam

New St John鈥檚 punt named in honour of evolution pioneer Louis Leakey

News
Vona Groarke in The Cloisters of St John's College, Cambridge
College writer shortlisted for TS Eliot poetry prize

Author among 10 established and new writers in running for 拢25,000 award hailed 鈥榳orld鈥檚 best poetry prize鈥

News
An aerial photo of St John's College, Cambridge
St John鈥檚 College unveils student development programme to tackle society鈥檚 biggest issues聽

鈥淲e have a long history of educating people who have changed the world鈥

News
An image of a cross-section of a mouse intestine
鈥楪ood鈥 gut bacteria boosts placenta for healthier pregnancy

Cambridge scientists discover how probiotics may help prevent miscarriages, gestational diabetes and preeclampsia

News
Research