Taking a hiatus from updates here, but more - including open positions in the SCBIR lab @TheCrick - over there 👉

Now out in print: https://t.co/ohMMteC276 See Maria's thread below for a nice summary of what we got up to and let us know if you'd be interested in trying out any of our new tools for probing the function of PAD4/PADI4

Check out this #OA review article, where Parkhill and @EachanJohnson explore potential routes to discover new antibacterial drugs, highlighting various classes of antibiotics, such as glycopeptides. #AMR #Microbiology #DrugDiscovery https://t.co/Dpnfw5wvRz

I'm delighted to share our recent article developing an approach to identify cyclic peptide binders of challenging protein targets directly in cell lysates - led by @catherine_hurd with GSK's @Jake_T_Bush and Andy Powell @TheCrick @impch

New from our lab @TheCrick , led by @BetkaRoe. A fun side project that tried to understand what happens when a chaperonin encounters a translating ribosome. https://t.co/2t0cpKIMKl

...and if you find this work exciting, we have fully-funded PhD/post-doc positions available @TheCrick! International, collaborative environment, terrific Science and plenty of training & career support at every stage. Do get in touch, more details here  https://t.co/iXHDZOUVnI

Check out this #OA review article, where Parkhill and @EachanJohnson explore potential routes to discover new antibacterial drugs, highlighting various classes of antibiotics, such as glycopeptides. #AMR #Microbiology #DrugDiscovery https://t.co/Dpnfw5wvRz

Beyond thrilled to present our first (!) work @TheCrick! A tour de force by @tobyandrews et al combining imaging, solid morphometrics, theory, perturbations to show how a developing heart grows and scales up its morphological complexity to keep beating... https://t.co/RghtQtmYxF

Discovery of new antimicrobial has been neglected by UKRI for a while. Probably the panels still think almost non-existent Pharmaceutical research programmes will deliver new antibiotics. Very short sighted.

Using lots of illustrative examples, we advocate using molecular genetics in harmony with phenotypic drug discovery. Let us know what you think! https://t.co/R8C0cn2LNK

Resistance mechanisms can act on chemical structure of drugs or compensate for their biological action. So we need more integrated approaches that understand both the biology and the chemistry of new drugs. We can't focus only on vulnerable targets 🧬 or only on safe chemistry 🧪

We found that new resistance could be modelled as an exponential decay, (Unimolecular reaction kinetics for the chemists, and exponential distribution for the statisticians). New antibacterials have a half-life of 12-15 years before resistance. How to beat this relentlessness?🤔

Excitingly, this is already happening, e.g. promising natural products from uncultivable bacteria and macrocyclic peptides representing new chemistry 🎉 But slowdown in discovery is only part of the explanation for why there is resistance against all antibacterials.

Streptomycin was relatively easy to discover, but daptomycin was only discovered after screening 10,000,000 isolates 🥲 We argue that to boost antibacterial discovery, we need to explore new chemical space to get away from those 39 antibacterial drug classes.

Before you @ me, of course reality is more subtle and complicated🫠 But this simplification is consistent with the Waksman platform of screening environmental isolates which has (generally) dominated antibacterial drug discovery.

Fitting the solution to the Problem to the historical discovery data, we can say that we are effectively sampling at random from a pool of 39 antibacterial drug classes, and we've almost discovered them all. (Run your own analysis here https://t.co/WUAr6UPzAO 🤓💻)

Actually, we found that the plateau in discovery of new antibacterial drugs can be explained entirely by the Coupon Collector's Problem, which describes scenarios like collecting football stickers or baseball cards, and the rate of expanding the collection of unique stickers.

We started with the historical discovery data from Paul Race's lab. https://t.co/CGc1YEsqst There's a gradual levelling-off in the rate of discovery since the ~1970s. Is it simply because big pharma has been abandoning the antibacterial discovery space? 🤔💰

The antibacterial drug resistance crisis is not news. To propose solutions, we need to know causes. Sidestepping the complex of science with social, economic, and political factors, we asked a simple question: Why is there now resistance against every antibacterial drug?😳