Raff PhD Medal Winner 2023
Luka Smalinskaitė
Originally from Lithuania, Luka obtained her BSc in Molecular Biotechnology from Heidelberg Univerisity, Germany (photo from LMB MRC). For her MPhil degree, she moved to the UK to work with Professor David Ron at the Cambridge Institute for Medical Research. She is now pursuing her PhD in the lab of Dr Ramanujan Hegde at the MRC Laboratory of Molecular Biology.
Luka’s PhD research helped to establish a new framework for explaining how multipass membrane proteins are inserted at the endoplasmic reticulum. These proteins are essential for substance and information transfer in cells, and if they are made incorrectly, it can lead to diseases such as cystic fibrosis and retinitis pigmentosa. The mechanism of such protein insertion was extrapolated based on experiments done with single-pass membrane substrates. It was proposed that transmembrane domains of multipass membrane proteins insert in the same manner as single-pass membrane proteins through the lateral gate of the Sec61 channel that opens into the ER membrane. This process was thought to be repeated for each transmembrane domain until the whole protein inserts. However, the mechanism remained untested for decades. Harnessing biochemical assays, Luka showed that multipass membrane proteins are inserted independently of the lateral gate by an additional machinery adjascent to Sec61. Multipass membrane substrates bind the intramembrane chaperone PAT complex as soon as they can reach it at the oposite side of Sec61’s lateral gate. The substrate is stabilised there, while the PAT complex wedges Sec61 to a conformation incompatible with opening of the lateral gate. Concomittantly, the GEL and BOS complexes are recruited to the substrate. The three complexes and the Sec61 channel form the multipass translocon, bounding a lipid-filled horseshoe-shaped cavity where emerging transmembrane domains insert and the protein can fold. Presumably, most multipass membrane proteins in the human genome use multipass translocon during their biogenesis for insertion and folding.
The research that led to this new experimentally validated model for multipass membrane protein insertion was done in collaboration with Robert Keenan’s lab at the University of Chicago and was recently published in Nature (https://doi.org/10.1038/s41586-022-05336-2).
In addition to working in the lab, Luka has multiple other responsibilities at the LMB. This year she is helping to organise the annual international student symposium. Furthermore, Luka is a trained mental health first-aider, always available to lend an ear to their colleagues. Back in her home country Luka contributed to Biology education for many years by developing problem questions for the National Biology Olympiad and pro bono tuition online during school closure due to the pandemic.
You can follow Luka @Luka_polyA on Twitter.
Luka will be awarded the Raff Medal and give a talk about her research during the next joint BSCB/Biochemical Society co-organised meeting Dynamic Cell V which will be held on 17-20 April 2023 at Loughborough University.
The BSCB PhD Award – Raff Medal was established in 2020 to recognise BSCB PhD students who have made outstanding contributions to UK/Ireland cell biology. The medal has been named after Professor Martin Raff who was the president of BSCB from 1992-1995. Martin was instrumental in setting up and running the first 4-year PhD graduate programme in Molecular Cell Biology at the MRC Laboratory for Molecular Cell Biology (LMCB) at UCL.