Achievements

The killer weapon of the immune system

Researchers in Biological Sciences at Birkbeck, in collaboration with a group at the Peter MacCallum Cancer Centre in Melbourne, have determined the structure of a protein assembly used by the immune system to kill unwanted cells. The immune system uses cytotoxic T lymphocytes and natural killer cells to act as executioners when it detects the presence of virally infected or cancerous cells.  The cytotoxic and killer cells contain small membrane parcels filled with the protein perforin, which can punch holes through cell membranes, along with the toxic granzyme enzymes. When an infected cell is detected, the killer cell latches onto it and ejects some of the membrane parcels with their toxic contents so that the perforin protein punches holes in the target cell membrane, through which the toxic granzymes enter, rapidly causing the target cell to die (Figure 1). The cytotoxic and killer cells are professional assassins that can kill many victims in rapid succession, briefly attaching, ejecting their lethal cargo, and then moving on to the next victim. Perforin is an essential protein for survival, and unfortunate individuals who lack functional perforin usually die of infection or cancer in early childhood. On the other hand, over active killer cells can also cause serious damage, by triggering inflammation and killing healthy cells.

A former postdoctoral researcher, Marina Ivanova (now at Imperial College), determined the perforin structure in the group of Professor Helen Saibil, and the paper has been published in Science Advances. Perforin is made as single protein molecules that are stored inside their membrane compartment until they are needed, but when they are released, they join up into rings of around 22 molecules and undergo a dramatic shape change in order to punch the hole through the target membrane. Two parts of the protein that are at first coiled up in the molecule extend and join up into the ring to punch through the membrane. This shape change is shown in Figure 2, with the part of the protein that makes the big change highlighted in pink.

Figure 3 shows two views of a perforin ring (multicoloured molecules) enclosing a hole in a cell membrane (shown as a pale blue slab). Now that we know the details of the pore structure, it will be possible to think about designing drugs to either enhance or prevent its activity. This could eventually lead to new therapeutics for certain autoimmune diseases and the condition familial hemophagocytic lymphohistiocytosis.

Ivanova, M.E., Lukoyanova, N., Malhotra, S., Topf, M., Trapani, J.A., Voskoboinik, I., Saibil, H.R. (2022) The pore conformation of lymphocyte perforin. Science Advances 8, eabk3147.

Posted by ubcg49z in Commentaries, News, Publications

Nobel Prize in Chemistry for Bio-Inspired Catalysts

The Nobel Prize in Chemistry in 2021 has been awarded to German Benjamin List and British David MacMillan.
Prof Stefan Howorka from the ISMB at UCL Chemistry explains: ‘The two researchers have developed a new class of catalysts that are inspired by Nature. Enzymes are widely used in biology as they initiate and specifically control biochemical reactions to achieve the desired stereochemistry while limiting the creation of undesirable by-products. Reconstructing these catalytic functions with smaller and cheaper synthetic units is of considerable scientific and industrial interest. Ideally, synthetic catalysts should also avoid precious metals such as platinum which are not environmentally friendly.
List and MacMillan succeeded independently of each other in developing efficient biomimetic and “green” catalysts. In the late 1990s, List wondered whether amino acids found in the enzymes’ active site would also be able to achieve part of the same catalytic role if added in isolation. As proof-of-principle, List tested the catalytic properties of proline and related compounds in an aldol reaction. The specific question was whether the use of a chiral proline would control the stereochemical outcome of the reaction. Indeed, the chirality of the catalyst controlled which enantiomer of the aldol products was formed.
MacMillan was working in the same field. MacMillan was motivated to develop new catalysts that avoid the widely used metals. Rather, he focused on environmentally harmless and inexpensive organic frameworks that contain -in addition to carbon- oxygen, nitrogen, sulphur or phosphorous. Similar to List, MacMillan also tested chiral versions of his organic catalysts but with a different reaction, the Diels-Alder cycloaddition. The reaction was successful as enantiopure products formed depending on the chirality of the catalysts.
Reflecting the catalysts’ composition and enantioselective control, MacMillan coined the term ‘asymmetric organocatalysis’ This new field has grown dramatically and develops simple, easy-to-manufacture and environmentally friendly catalyst. This has a huge impact in science and industry to produce new pharmaceuticals or molecules that can capture light in solar cells. This year’s Nobel prize and the Nobel prize given in 2018 for ‘the directed evolution of enzymes’ underscore the importance of developing new catalytic tools, Prof Howorka concludes.

References:
J. Am. Chem. Soc. 2000, 122, 2395-2396; J. Am. Chem. Soc. 2000, 122, 4243-4244

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EMBO Fellowship Successes!

Dec 2020: Postdoctoral EMBO fellowships awarded to ISMB postdoc Sander Van der Verren and former ISMB PhD student Joshua Hutchings.

ISMB’s Sander Van der Verren has been awarded a prestigious and highly competitive EMBO fellowship to work at ISMB in Giulia Zanetti’s laboratory. The fellowship will support structural studies of the human COPII coat complex and its regulatory factors. COPII mediates vesicular transport of proteins out of the Endoplasmic Reticulum, and its regulation in humans is important for secretion of a wide range of cargoes, including the most abundant secretory proteins: collagens. As part of the Birkbeck cryo-EM lab, Sander will use cryo-tomography and single particle cryo-EM techniques to understand how regulatory factors TANGO1 and cTAGE5 assemble and interact with the coat to promote collagen secretion.

Sander says: “I am honoured to have been awarded an EMBO postdoctoral fellowship and look forward to tackle outstanding questions in the membrane trafficking field.”

A Zanetti lab recent alumnus, Josh Hutchings, was also successful in securing an EMBO fellowship. His postdoctoral studies in Elizabeth Villa’s lab at UC San Diego will focus on in situ characterisation of the LNK complex.

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Prof. Sanjib Bhakta wins prestigious Microbiology Society 2020 outreach prize

The Microbiology Society Outreach Prize 2020 was awarded for the charity project ‘Joi Hok’, which uses educational intervention as a means of spreading awareness of tuberculosis.

Professor Sanjib Bhakta, Professor of Molecular Microbiology and Biochemistry at the ISMB and ‘Joi Hok!’ founder Sreyashi Basu have been awarded the 2020 Microbiology Outreach Prize by the Microbiology Society, for effectively bridging the gap between laboratory science and public health research with their project ‘Joi Hok!’, a community tuberculosis (TB) awareness programme.

The programme’s aim is to alter the perception of TB among the local community in Kolkata, India, through a network of local artists, musicians and health professionals. A series of routine interdisciplinary workshops were introduced in semi urban and rural schools around the city over a span of 6 months.

Sanjib Bhakta commented: “TB has progressively worsened with the advent of antibiotic resistance, hence there is urgent need to review and deal with the disease not only as a medical concern or even public health problem alone, but also as a socio-economic challenge.”

Sreyashi Basu commented: “we used traditional folk-art and music as a creative tool to engage and educate underprivileged youth on the influence of local stigmas and antibiotic resistance in the context of TB. We have been fortunate to see a discernible impact amongst the masses whereby the transfer of knowledge from children to household members has resulted in an increased awareness of TB in the community and encouraged patients to adhere to anti-TB treatment regimens .”

Professor Mark Harris, General Secretary of the Microbiology Society, said: “The Microbiology Society Prizes panel felt that the ‘Joi Hok!’ tuberculosis awareness programme demonstrated an inventive and exciting approach to informing the public about an important disease.  The novelty of the programme was its innovative use of traditional art and music to raise awareness of tuberculosis in rural India, with potential to positively influence treatment and control in a country that has the highest global incidence of this devastating infection – a worthy winner of the Microbiology Society Outreach Prize 2020.” 

The Microbiology Society is a membership charity for scientists interested in microbes, their effects and their practical uses, and is one of the largest microbiology societies in Europe. The Microbiology Outreach Prize is awarded for an outstanding outreach initiative, that shows innovation, originality and a sustained impact over time.

The Joi Hok programme uses traditional art and music to raise awareness of Tuberculosis in rural India.
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Prof. John Christodoulou awarded the British Biophysical Society’s 2020 Sosei Heptares Prize

Congratulations to Prof. John Christodoulou (jointly affiliated between UCL and Birkbeck in the ISMB), on being awarded the British Biophysical Society’s 2020 Sosei Heptares Prize for Biophysics. The prize is in recognition of Prof. Christodoulou’s original and influential contributions to the advancement of biomolecular NMR and the biophysical analysis of protein folding on the ribosome.

John is serving as the director of the NMR facility at the ISMB and has been a driving force behind high-calibre structural biology at the ISMB for more than twelve years.

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Prof. Bonnie Wallace wins the RSC Khorana Prize 2020

Congratulations to Professor Bonnie Ann Wallace for winning the Royal Chemical Society’s Khorana Prize 2020.

This prestigious accolade is awarded for her pioneering development of biophysical methods and bioinformatics tools to enable the characterisation of ion channel-drug molecule complexes. The Khorana Prize is the latest marker of esteem reflective of a highly successful career, as Bonnie also received the RSC Interdisciplinary Prize 2009 and the Biochemical Society’s AstraZeneca Award 2010.

Further details about the award are available here.

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Gorjan Stojanovski and Hugo Villanueva win prizes at ISMB Graduate Symposium

Congratulations to Gorjan Stojanovski and Hugo Villanueva, who were awarded prizes for their research presentations at this year’s ISMB Graduate Symposium. The Symposium was held in the Clore Management Centre at Birkbeck on Thursday 25th and Friday 26th April.

Gorjan, from Professor John Ward’s group, presented on ‘Applying bacterial competition to evolve novel antibiotics.’

Hugo, from Dr. Renos Savva’s group, presented on ‘Refactoring phages as repurposed nanomachines.’

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Birkbeck Department of Biological Sciences receives Athena SWAN Silver Award

The Department of Biological Sciences, Birkbeck has been awarded an Athena SWAN Silver Award by the Equality Challenge Unit (ECU), upgraded from its previously held Bronze Award. The award recognises the department’s commitment to achieving gender equality across the institution and the progress that it is making in this area. It is valid until April 2022.

The ECU presents Athena SWAN awards to recognise and reward commitment to gender equality in higher education. Its Charter was established in 2005 to encourage and recognise commitment to advancing the careers of women in science, technology, engineering, maths and medicine (STEMM) employment in higher education and research.
In 2015, the charter was expanded to recognise work undertaken in arts, humanities, social sciences, business and law, and in professional and support roles, and for trans staff and students. The charter now recognises work undertaken to address gender equality more broadly, and not just barriers to progression that affect women.

The Department of Biological Sciences’ Athena SWAN Silver Award was formally presented at a ceremony at the University of Southampton on 10 December 2018.

 

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ISMB’s Dr Alan Cheung and Dr Anthony Roberts selected as EMBO Young Investigators

ISMB members Dr Alan Cheung and Dr Anthony Roberts have received the prestigious EMBO Young Investigator Award in recognition of the outstanding quality of their current work and their proposals for future research.
The EMBO Young Investigator Programme identifies recent group leaders with a proven record of scientific excellence.
In the most recent round of applications the programme received 195 eligible applications out of which 26 young researchers were selected to join an active network of 102 current Young Investigators.
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