Lightnews — Scholar-powered news

Elisa Fadda

@elisafadda.bsky.social

"It is not a stretch to say that every pharmaceutical company now studying cancer, HIV-AIDS, COVID-19, and a host of other diseases has made use of Jorgensen’s water models."

As we all do, 45k citations and counting! 👏🏻👏🏻👏🏻

news.yale.edu/2025/11/18/d...

The original manuscript for Jorgensen’s seminal study.

November 25, 2025 at 7:30 AM

Elisa Fadda

@elisafadda.bsky.social

Always remember Monty Don's words of wisdom:

"Perhaps in the end all gardening boils down to this: do not fight Nature because, however brilliant a gardener you think you are, you will always lose"

(e.g. me looking up at my beautiful beech while raking the lawn)

Yellow and orange beech leaves against the blue sky.... All about to fall on me while I rake then underneath

November 24, 2025 at 8:48 AM

Elisa Fadda

@elisafadda.bsky.social

Southampton #parkrun in the blistering sunshine 😎🕺🏻

Southampton common pond blue sky fluffy clouds trees with yellowing leaves all around

Selfie after the funnel, blue shirt black cap and specular sunnies

November 8, 2025 at 9:57 AM

Elisa Fadda

@elisafadda.bsky.social

Stunning sunshiny morning for a #parkrun in the Southampton Common 😎☀️

Sun and sky (with a few fluffy white clouds) reflecting on the pond in Southampton Common shadow of the trees in dark green/black

Selfie at the end of parkrun red shirt, Tenerure 5m in 2015!!!! And black cap green grass all around

October 25, 2025 at 4:53 PM

Elisa Fadda

@elisafadda.bsky.social

Salem is trying really hard, but he needs to clean his paws first... 🙄😎

Black cat with green eyes laying on the carpet with dirty paws

October 22, 2025 at 7:22 PM

Elisa Fadda

@elisafadda.bsky.social

I usually leave my garden flowers to the bees, as I don't have heaps (yet), but the gorgeous purple dahlia from Schiphol Airport is starting to fade so I thought I should continue to celebrate its beauty for a wee bit longer 💐😍 #gardening

And for #glycotime friends, fans of sialic acid, rejoice 💜

Bouquet of light purple, pink and deep purple flower bouquet in a glass vase, including dahlia, cosmos, lavender, mini carnations and daisies (different types I don't know the names of 😜) all from my garden

October 11, 2025 at 1:38 PM

Elisa Fadda

@elisafadda.bsky.social

For movie night (if you need inspo) is All the President's Men, an absolute classic always worth another go 🍿📽️

Poster for the movie All the President's Men with Dustin Hoffman (left) and Robert Redford (right)

October 10, 2025 at 7:24 PM

Elisa Fadda

@elisafadda.bsky.social

Snap! I think I wrote something precisely along those lines after seeing the doc Endurance, which is truly stunning! also went to the south pole pub in Annascaul to pay homage to a true explorer and hero, Tom Crean mentioned only in passing in the doc

films.nationalgeographic.com/endurance

The sign at the entrance of the South Pole pub reads this pub may contain nuts

Sign posting Ernst Shackleton's as in the paper to recruit volunteers for the Endurance voyage. Reads "Men wanted for hazardous journey small wages, bitter cold, long months, safe return doubtful. Honour and recognition in case of success"

October 10, 2025 at 1:52 PM

Elisa Fadda

@elisafadda.bsky.social

"Characterization of the synthetic G-X6-G TM protein family revealed a range of folding free energies and characteristic interhelical Cα-H∙∙∙O = C H-bonds. Van der Waals (vdW) sidechain packing at ancillary interacting positions as the dominant molecular feature"

www.pnas.org/doi/10.1073/...

De novo design of minimal idealized G-X6-G TM proteins. (A) Motif of close antiparallel TM helices in membrane proteins using G-X6-G repeats (white cartoon); glycines, purple sticks or red Cα spheres; yellow dash, Cα-H hydrogen bonds. PDB codes Left to Right: 6LEO, 7C83, 4ZP0, 8SRN. (B) A design model is broken into fragments centered around each interface amino acid (AA), at a and “d-e” packing layers (red and purple Cα spheres, respectively). Natural membrane protein structures (SI Appendix, Table S1) are data-mined for instances of similar local helix–helix geometries, collecting corresponding primary sequences to compile a structure-based MSA. Packing layers represented in a graph-based network (Right) are sampled to statistically infer new de novo TM protein sequences from the MSA data. (C) Models of de novo antiparallel G-X6-G TM homodimer complexes overlaid with ESMfold predicted structures (pLDDT > 0.8). N and C termini are labeled blue and red, respectively.

October 9, 2025 at 12:34 PM

Elisa Fadda

@elisafadda.bsky.social

In memory of a wonderful, kind, lremarkable and infinitely inspirational human. Che la terra le sia lieve 🖤 #RIPJaneGoodall

Screenshot of the BBC announcement of the death of Jane Goodall 1934-2025

October 1, 2025 at 8:10 PM

Elisa Fadda

@elisafadda.bsky.social

The most wonderful time of the year @unisouthampton.bsky.social 😍🪴🌵

Two green leafy plants on the window sill (my office). Left a dracaena in a brown vase and right a fiddle leaf fig

Sign yellow with black writing "houseplant sale today students union

October 1, 2025 at 12:16 PM

Elisa Fadda

@elisafadda.bsky.social

All ready to start our sparkling new BIOL6105 module Advanced Pharmacology 🥳🥳 for our sparkling new MSci Pharmacology and Drug Discovery programme at @sotonbiosciences.bsky.social @unisouthampton.bsky.social

And now, let's Fold.it!! @foldingathome.org

Computer room ready for our students, blue screens showing title slide reading BIOL6105 Advanced Pharmacology

October 1, 2025 at 7:53 AM

Elisa Fadda

@elisafadda.bsky.social

Salem likes very much his tension swatches especially as a #Caturday treat 🥳🥳 (for 2 minutes at least....)

Salem (black cat) enjoying his stringy tension swatch (pink wool) on the carpet (beige) for some Caturday fun

September 20, 2025 at 10:50 AM

Elisa Fadda

@elisafadda.bsky.social

The practice of punishing students for using ChatGPT, while on the same breath saying 'I only use it for xyz (add whatever, heard it all), because I am amazing and I use it judiciously' 🤔🤔

This today's thought and (as a note) I do hate ChatGPT (whichever) with a passion ☺️

September 18, 2025 at 7:01 PM

Elisa Fadda

@elisafadda.bsky.social

Here I am, free soloing top predator of this house 🦖, on the hunt for the juicy 🦟 that are not bleeding the photographer dry...

Baby geckos are some beauty 😍😍🦎 #sardinia

Baby gecko (grey/greenish/black) seen from behind, exploring the white wall surface on a mission to find some delicacy for breakfast

September 13, 2025 at 7:25 AM

Elisa Fadda

@elisafadda.bsky.social

#badglycans sialylated Asn 😱😱

"These data suggests that inhibition of ACO2 activity, through sialylation of Asn 612, is because of major distorsions of the active site..."

Pls revise to:

"This figure and conclusions suggest that none of the reviewers read the manuscript"

Snapshot of a highly distorted sialic acid 'docked' onto Asn612 in the binding site of a protein. All rendered in sticks

September 11, 2025 at 5:57 AM

Elisa Fadda

@elisafadda.bsky.social

@beatricetropea.bsky.social presenting our new work with @benschulz.bsky.social (fresh 2-hand 🧵 below ⬇️) on the regulation of N-glycosylation efficiency by eukaryotic OST @CECAM meeting in Cagliari, Italy 🎉😎

Beatrice Tropea left starting her presentation on the screen in the podium

September 9, 2025 at 10:27 AM

Elisa Fadda

@elisafadda.bsky.social

@joel-allen.bsky.social and ‪@maxcrispin.bsky.social identified the unoccupied site in a human Fab has sequence IGEINHSGK, remarkably similar to our ‘forbidden’ sequence. This has 0 occupancy and specific seq variations at and around the sequon control occupancy matching the proposed mechanisms...

(a) Percentage occupied (%Occ) and un-occupied (%Unocc) by N-glycosylation at Asn57 for each Fab, as determined by LC-MS. Extended sequence context of Fabs centered at Asn57 with the classical NxS/T sequon in bold. Residues with negative charge (glutamate) are blue, positive charge (lysine) are pink, and aliphatic residues (isoleucine, valine and alanine) are beige. (b) Crystal structures of previously reported FL14 Fab (PDB submission pending) and 10531 Fab resolved to 1.76 Å, containing solvent-exposed, but unoccupied, Asn57. The final 2Fobs-Fcalc electron density maps (contoured at 1.1 sigma) are shown for the extended Asn57 sequons and coloured as in (a). Density is also shown for occupied glycosylation sites in each Fab (Asn38 for FL14, and Asn110 for 10531).

September 9, 2025 at 7:58 AM

Elisa Fadda

@elisafadda.bsky.social

To identify the signatures for unglycosylatable sequons we screened secreted protein sequences in the human proteome with a solvent inaccessible structure at the site (PDB/AF) totalling 997 sequons. The representative sequence in buried sequons showed enrichment in IGEINH[S/T][W/G]N

(h) Amino acid enrichment across the –4 to +4 region surrounding buried canonical sequons (internal sequons). Letter height reflects the ratio between observed and expected frequencies based on vertebrate background distributions. Enrichment of turn-promoting residues such as His and Trp at position +1 supports a conformational mechanism that disfavors glycosylation. Plots were generated using Matplotlib v3.8.4.

September 9, 2025 at 7:53 AM

Elisa Fadda

@elisafadda.bsky.social

The optimal binding of a peptide sets ON a molecular switch that releases the assisting base for catalysis. Results of free energy calculations show that efficiently glycosylated substrates favour the ON position, while substrates always underglycosylated favour the OFF position

(a) Close-up view of the OST structure in complex with a substrate mimetic rendered in cyan cartoons (PDB 8AGC). Labels indicate positions from -1 to +2 along the substrate. Key catalytic residues are labelled and rendered with sticks with C atoms in green, N atoms in blue and O atoms in red. In this structure the switch is defined as “OFF” as the catalytic base Glu 350 is engaged in a salt bridge with Arg159. Asp47 is the catalytic nucleophile. (b) Representative snapshot from the equilibrated conformation of the complex between the OST model and the efficiently glycosylated YJR1_N99, corresponding to 520 ns of the 1 μs trajectory. The presence of an active substrate in the binding site with the Asn acceptor in a productive configuration displaces the Glu350 for the reaction to proceed, releasing Arg159 to form a salt bridge with Glu 45, switching ‘on’ the OST. (c) Close up view of the OST switch in the ON state from the snapshot from the OST/YJR1_N99 MD trajectory at 520 ns. The Mn2+ ion is not represented for clarity. The carbonyl of the residue at -2 triggers the opening of E350-R159 salt bridge in the resting OFF state by electrostatic repulsion with the carboxylate of E350, located 3.72 Å away in this frame. (d) Potential of mean force (PMF) rendered with spline regression, calculated for the OST in complex with PLB2_N193 (grey; efficiently glycosylated), GAS1_N40 (green) and ECM33_N328 (yellow) (both underglycosylated under stress), and PLB2_N365 (pink; never glycosylated). The labels ON (green) and OFF (red) indicate active and inactive orientations of the Arg159 sidechain, respectively, corresponding to values between 120°–145° (for ON), and 210°–240° (for OFF). Molecular structures rendered with Visual Molecular Dynamics21 (VMD) (https://www.ks.uiuc.edu/Research/vmd/). PMF data visualization rendered with seaborn FacetGrid (https://seaborn.pydata.org/).

September 9, 2025 at 7:46 AM

Elisa Fadda

@elisafadda.bsky.social

Thank you Ben 🤩 The amazing Beatrice Tropea selected a set of representative substrates from Ben’s screening panel and identified that OST binding is regulated by interactions ‘beyond the sequon’ along a -4 to +4 stretch of the substrate’s sequence localised in regions we named Pocket 1 to 3...

(a) 3D structure of the yeast OST built from cryo-EM structure (PDB 8AGC) with the Ost3 lumenal domain rebuilt with AlphaFold 2. The domains included in the MD model of the OST are shown in yellow within a representative (equilibrated) structure from the MD simulation in complex with the peptide YJR1_N99, shown in cyan as cartoons. The lipid bilayer representing the ER membrane in the simulation is rendered with green sticks. (b) Sequences of selected peptides used as substrates for the MD simulations. (c) Close-up view of the extended OST binding groove showing how the aromatic sidechain of Phe 96 at position -3 of the acceptor peptide substrate, shown in cyan, is accommodated in a cavity (Pocket 1). (d) The residues of Stt3 and Ost3 lining the hydrophobic interior and the hydrophilic rim of Pocket 1 are shown as sticks with C atoms in yellow, N atoms in blue and O atoms in red. The Stt3 and Ost3 backbone is shown in grey with cartoon rendering. (e) Residues of Stt3, rendered with sticks, within the region identified as Pocket 2 accommodating residues at position -1 from the peptide sequon. Glu 45 and Arg 159 are part of the ‘switch’. (f) Residues of Stt3, shown with sticks, within the region identified as Pocket 3 accommodating residues at position +1 from the peptide sequon. Residue numbering follows PDB 8AGC.

September 9, 2025 at 7:40 AM

Elisa Fadda

@elisafadda.bsky.social

A few come to mind, but this was a game changer ⬇️

September 8, 2025 at 5:17 AM

Elisa Fadda

@elisafadda.bsky.social

My stash of 🇦🇺 literature this time includes 3 mystery novels! This one ⬇️ is excellent! A fast-paced page turner, set deep in the Queensland outback, embedded in the drama of aboriginal land and culture loss and in the unequal value placed on the lives of aboriginal people. Highly recommended! 📚♥️