CFBD researchers are again invited to apply for a CFBD Travel Grant to the value of up to $3,500. This grant may be used for travel to a national or international conference, a visit to a partner organisation for research collaboration or a visit to a research laboratory to learn a new technique. The CFBD TravelGrant is an annual award.
CFBD members Karol Sanches, Yildiz Tasdan and Jack Phelps (all Monash) have started their international placements as part of their ARC scholarships. While Karol has already completed her placement with TetraGenetics in Boston (USA), Yildiz and Jack are working at Vernalis in the UK. Here, Jack talks about his experience during his first couple of weeks:
“How time flies! It still feels like yesterday that I was saying goodbye to Melbourne and flying home to the UK to start my placement at Vernalis, Cambridge. I’ve now somehow been here for 3 months and am loving the experience of working in the industry. Of course, there are similarities (every day starts with coffee before setting up experiments), but also many notable differences. As expected (but slightly annoyingly) there’s a real sense that money, not discoveries themselves, is the driving force behind each project here, and when talking about my work it’s difficult to describe the end goal in terms of industry buyouts (which feels a long way off yet!). On a more personal note, the most exciting difference for me is on the technology side: All the columns are automatic and can be monitored remotely from your desk! Luckily, this is the case in protein purification too, as I’ve become much more of a biologist over the past couple of months. This brings me to the other major new experience in industry – not having to make up LB or wash/autoclave your own glassware! Call it laziness if you’d like, but I prefer to think of it as more time to spend doing the science… As well as protein science, I’ve also been fortunate enough to model protein sequences using AlphaFold and to start exploring crystallography. All this being said though, I’m still missing the people at MIPS that kept me going during my PhD. With all the new helpful technicians and processes, there’s no substitute for the community of students and the city of Melbourne.”, Jack Phelps (Monash)
We will post more updates from Karol and Yildiz soon. Stay tuned!
The 2022 FBDD DU Conference proved to be a huge success for CFBD members. We heard fantastic presentations from the plenary speakers and fascinating stories from the presenters with a good number of Centre members represented. We saw brilliant posters and made new connections during the networking sessions. Adding to this, our members hit the jackpot with the FBDD DU presentation prizes. Congratulations to:
Louise Sternicki (Griffith) for winning the Best ECR Oral Presentation Award
Jeyan Osman (Monash) for winning the Best Student Presentation Award
Yildiz Tasdan (Monash) for winning the Student Presentation – Runner-Up Award
Max Lumetzberger (Monash) for winning the Best Poster Presentation Award
Evgenia Konstantinidou (Monash) for winning the Poster Presentation – Runner-Up Award
Compounds Australia, through Therapeutic Innovation Australia (TIA), is part of the National Collaborative Research Infrastructure Strategy (NCRIS), a network of world-class research infrastructure facilities that drives and supports greater innovation in the Australian biomedical research sector and associated economic impact. Recently, CFBD CI Prof Sally-Ann Poulsen was appointed as acting Director of Compounds Australia. Curating Australia’s largest collection of compounds and natural products (~1.5M), Compounds Australia supports 38 national/international member organizations and >250 research projects annually, including the fragment screening campaigns of the CFBD. Monash University, University of Sydney and Griffith University are all member organizations. CFBD CI Prof Jonathan Baell is an existing Advisory Board Member of Compounds Australia. Many of the fragment libraries that are used by the Centre are currently managed by Compounds Australia. Congratulations to Sally-Ann on this excellent new role.
We are delighted to welcome The Australian Nuclear Science and Technology Organisation (ANSTO) as our new Industry Partner to the Centre. ANSTO, Australia’s knowledge centre for nuclear science and engineering, leverages great science to deliver big outcomes. ANSTO partners with scientists and engineers and applies new technologies to provide real-world benefits. Their work improves human health, saves lives, builds our industries, and protects the environment. ANSTO is the home of Australia’s most significant landmark and national infrastructure for research. Thousands of scientists from industry and academia benefit from gaining access to state-of-the-art instruments every year.
Please join us in welcoming Dr Rachel Williamson and Dr Alan Riboldi-Tunnicliffe as our new Partner Investigators. You can also meet them in person at our Joint ANSTO & CSIRO workshop on 12 August 2022. Don’t forget to register your interest with the Centre Manager.
Not one but five CFBD members from our three nodes published a paper on DsbA titled “Identification and characterization of two drug-like fragments that bind to the same cryptic binding pocket of Burkholderia pseudomallei DsbA” in Acta Crystallographica Section D.
Disulfide-bond-forming proteins (Dsbs) play a crucial role in the pathogenicity of many Gram-negative bacteria. Disulfide-bond-forming protein A (DsbA) catalyzes the formation of the disulfide bonds necessary for the activity and stability of multiple substrate proteins, including many virulence factors. Hence, DsbA is an attractive target for the development of new drugs to combat bacterial infections. Here, two fragments, bromophenoxy propanamide (1) and 4-methoxy-N-phenylbenzenesulfonamide (2), were identified that bind to DsbA from the pathogenic bacterium Burkholderia pseudomallei, the causative agent of melioidosis. The crystal structures of oxidized B. pseudomallei DsbA (termed BpsDsbA) co-crystallized with 1 or 2 show that both fragments bind to a hydrophobic pocket that is formed by a change in the side-chain orientation of Tyr110. This conformational change opens a `cryptic’ pocket that is not evident in the apoprotein structure. This binding location was supported by 2D-NMR studies, which identified a chemical shift perturbation of the Tyr110 backbone amide resonance of more than 0.05 p.p.m. upon the addition of 2 mM fragment 1 and of more than 0.04 p.p.m. upon the addition of 1 mM fragment 2. Although binding was detected by both X-ray crystallography and NMR, the binding affinity (Kd) for both fragments was low (above 2 mM), suggesting weak interactions with BpsDsbA. This conclusion is also supported by the crystal structure models, which ascribe partial occupancy to the ligands in the cryptic binding pocket. Small fragments such as 1 and 2 are not expected to have a high energetic binding affinity due to their relatively small surface area and the few functional groups that are available for intermolecular interactions. However, their simplicity makes them ideal for functionalization and optimization. The identification of the binding sites of 1 and 2 to BpsDsbA could provide a starting point for the development of more potent novel antimicrobial compounds that target DsbA and bacterial virulence.