Alejandra Tomas

Thanks to all the coauthors, particularly Denise Wootten and Giuseppe Deganutti for the cryo-EM and MD simulations, and the first author, former PhD student Liliane El Eid

Ongoing, unpublished work further suggests behavioural alterations and changes in body fat distribution in the A316T variant mice, which we are now actively investigating.

characterised by increased microsteatosis. This was linked to reduced glucagon secretion, plasma aminoacidosis, and α‑cell hyperplasia, highlighting that constitutive GLP‑1R activation is not universally beneficial.

which led to reduced surface expression of the variant receptor, explaining the heightened desensitisation associated with this constitutively active receptor variant.
Unexpectedly, when challenged with a high‑fat diet, A316T mice developed an adverse hepatic phenotype...

particularly ligands that are not biased away from β‑arrestin recruitment. This pointed to increased basal signalling and enhanced receptor desensitisation effects. Mechanistic studies in islets from these mice, as well as in rat and human β‑cell models, revealed increased lysosomal trafficking...

In parallel, we resolved the cryo‑EM structure of GLP‑1R A316T variant, providing structural insight into its altered signalling behaviour. Despite improved glucose tolerance and reduced weight gain under a high fat diet, A316T mice were largely unresponsive to pharmacological incretin therapies,

I am delighted to report that our latest paper has now been published in Science Advances:
www.science.org/doi/10.1126/...
In this study, we generated and characterised a humanised GLP‑1R mouse model carrying the gain‑of‑function A316T variant using CRISPR/Cas9 knock‑in technology.

Our review on GLP-1R signal compartmentalization is now out in JCI, where we discuss current evidence for the existence of GLP-1R–cAMP–PKA signalosomes at different subcellular locations and the complexity of the GLP-1R spatiotemporal signaling architecture:
www.jci.org/articles/vie...

Many thanks David, here is to many more collaborations on our favourite receptors and cells!

I’m delighted to share that I have been promoted to Professor of Cell Biology at Imperial College London. I am deeply grateful to those who have supported me along the way, through the many ups and downs that led to this point.

And a new paper from our group now published in DOM on a novel dual GLP-1R/GIPR agonist with improved action in vivo
doi.org/10.1111/dom....

Glycaemic and bodyweight effects of GIPR coding variation reflect differences in both surface expression and intrinsic functional impairment The glucose-dependent insulinotropic polypeptide receptor (GIPR) is the target of several approved and investigational drugs for type 2 diabetes and obesity. Missense coding variation in GIPR could co...

Our newest study looking at the impact of missense GIPR variants in BMI versus glycemia, receptor stability, and pancreatic islet function.
www.medrxiv.org/content/10.1...
A collaboration of Imperial College with Eli Lilly and University of Cambridge.

Still time to apply to this Lectureship position in our Section. Deadline 25th March.

Congratulations to Liliane ElEid who successfully passed her PhD viva yesterday! Here are some pictures of the post-viva celebrations. Many thanks to Prof David Hodson @daveyboyhod.bsky.social and Dr Bryn Owen for assessing her thesis and to David for his visit and Seminar.

GLP-1R associates with VAPB and SPHKAP at ERMCSs to regulate β-cell mitochondrial remodelling and function Glucagon-like peptide-1 receptor (GLP-1R) agonists (GLP-1RAs) ameliorate mitochondrial health by increasing mitochondrial turnover in metabolically relevant tissues. Mitochondrial adaptation under met...

Our newly revised manuscript on ER-mitochondria membrane contact site-localised GLP-1R signalling hub now out in bioRxiv: www.biorxiv.org/content/10.1...

Description Please note that job descriptions are not exhaustive, and you may be asked to take on additional duties that align with the key responsibilities ment...

Are you interested in developing a research programme in cell biology of diabetes? Do you work in pancreatic islets and/or other metabolically relevant cells? We have a Lectureship post opening in our Section @imperialcollegeldn.bsky.social
Apply by 25th March:
www.imperial.ac.uk/jobs/search-...

Binding Kinetics, Bias, Receptor Internalization and Effects on Insulin Secretion in vitro and in vivo of a Novel GLP-1R/GIPR Dual Agonist, HISHS-2001 The use of incretin analogues has emerged in recent years as an effective approach to achieve both enhanced insulin secretion and weight loss in type 2 diabetes (T2D) patients. Agonists which bind and...

Our newest preprint about a new GLP-1R/GIPR dual agonist:
www.biorxiv.org/content/10.1...

Last few days to apply for a postdoc position in my lab

Our collaboration with the talented Sarah Rouse now out in bioRxiv:
"Human class B1 GPCR modulation by plasma membrane lipids"
www.biorxiv.org/content/10.1...

Still time to apply to this position! Application open until 15th Jan 2025.

The physiological impact of an N-terminal Halo-tag on GIPR function in mice Aims: G protein-coupled receptors (GPCRs) modified with self-labelling enzymatic tags (e.g. Halo, SNAP, CLIP) have enabled the in vitro study of receptor expression and trafficking. We developed a Gip...

Our attempt to tag endogenous GIPR in vivo with a Halo-tag

www.biorxiv.org/content/10.1...

Deciphering the metabolic regulation of inflammasome activation at Imperial College London on FindAPhD.com PhD Project - Deciphering the metabolic regulation of inflammasome activation at Imperial College London, listed on FindAPhD.com

PhD Studentship available in the lab of Dr Paras Anand at Imperial, in collaboration with me:
www.findaphd.com/phds/project...

A postdoctoral position is available in my lab to study the subcellular organisation of signalling of the glucagon receptor family. For more information and to apply please click here: www.imperial.ac.uk/jobs/search-...