By Meredith Wright
From September 5-8, scientists converged on Birmingham, UK for the 6th European Molecular Biology Organization Meeting. EMBO is an organization which aims to support multiple branches of science, by holding courses, workshops, conferences, and publishing the EMBO journal. This year’s meeting consisted of a diverse array of speakers, as well as varied career development sessions. The meeting had three sets of plenary lectures; here, we highlight the speakers and their work from the ‘Pathogens and Defense’ set from Sunday, Sept. 6th.
PLOS had a booth at the EMBO meeting, and PLOS Student Blogger Meredith Wright recaps some of the key speakers from the 2015 meeting.
Griffiths is the director of the Cambridge Institute for Medical Research and Professor of Immunology and Cell Biology at the University of Cambridge. Her lab studies the immunological synapse; that is, the site of interaction between cytotoxic immune cells (such as T cells or NK cells) and antigen presenting cells. The immunological synapse can be compared to the more widely-known neuronal synapse in that these are both locations where adjacent cells can communicate. However, the neurons making up a synapse in the brain do not touch, and rather transmit signals via diffusible factors. Meanwhile, the immunological synapse is a true cell-cell junction, with both secretion of diffusible factors and binding of the two cells via cell surface receptors. Specifically, the immunological synapse consists of a central cluster of T cell receptors surrounded by adhesion molecules and further surrounded by an actin ring. These structures work together to very specifically secrete effector molecules to only the target cell, with the goal of killing the infected target cell.
The precise mechanics of the formation of the synapse remains an active area of research. The most recently published work from the Griffiths lab looks at granule secretion at the immunological synapse. They used high-resolution 4D imaging to study the timing and order of the key events that lead to secretion of cytotoxic granules during immunological synapse formation. The microscopy techniques used are as impressive as the actual results, as the “4D” imaging is achieved by utilizing multiple types of microscopy (spinning-disc confocal microscopy and lattice light-sheet microscopy capture multiple components of cytotoxic cells over time).
Holden is the Director of the MRC Centre for Molecular Biotechnology at the Imperial College London. His lab studies bacterial virulence mechanisms primarily in the Salmonella bacterium. Salmonella is a genus of bacteria known for being a major cause of food poisoning, with Salmonella enterica being the particular species responsible for most human disease. S. enterica has a number of virulence factors, but it is perhaps most famous for its two Type III secretion systems. The T3SS is a secretion system that functions like a molecular needle; it injects effector proteins into the target-cell cytosol, which then alter signaling in the host cell to the benefit of the bacterium. The details of how and when the T3SS is of use to the bacterium are not completely understood, and the molecular mechanisms of the many different effector proteins are also still being studied.
The Holden lab is currently studying the effectors translocated by the T3SS encoded on Salmonella pathogenicity island 2 (SPI-2). This T3SS is essential for the bacterium to maintain the Salmonella-containing vacuole inside infected cells. Recent work from the lab shows that Salmonella effector SifA interferes with the lysosomal adaptor Pleckstrin homology domain-containing protein family member 1 (PLEKHM1). Depletion of PLEKHM1 leads to defective Salmonella-containing vacuole formation, which they term a “bag of Salmonella,” and reduced Salmonella growth. In addition to this work with effectors, the Holden lab has recently shown that Salmonella is able to induce changes to host cells that are associated with gallbladder carcinoma. This has global health implications, as this indicates that parts of the world where S. enterica infections are extremely common are at a higher risk for gallbladder cancer.
Carrington is the Director of the Basic Science Program at the Frederick National Laboratory for Cancer Research at the National Institutes of Health in the United States. Her work focuses on the connection between human leukocyte antigen (HLA) class I genes and human immunodeficiency virus (HIV) infection. It is already known that variation in HLA class I genes can lead to different outcomes of HIV infection; that is, certain HLA alleles result in slower progression from HIV infection to AIDS. However, work in her lab is demonstrating that variation near the HLA class I genes and in the regulation of the HLA class I genes also plays an important role in HIV infection.
For example, in a 2014 PLOS Genetics paper, her lab showed that polymorphisms in the HLA class I genes can alter how innate immune cells fight HIV. Specifically, different HLA-B alleles have different binding capabilities with leukocyte immunoglobulin-like receptors (LILR), which are found on dendritic cells. Binding strength of LILR to HLA class I types in patients positively associated with viral replication. More recently, her lab studied the connection between HLA class I and HIV in pediatric versus adult patients, and surprisingly found that the protective effects granted by some HLA genes in adults are not present in pediatric patients. This further supports the lab’s assertion that HLA class I allele alone cannot predict HIV outcome for all patients, and that additional work on nearby/regulatory genes is needed.