Conference on retroviruses and opportunistic infections (virtual): March 6–10, 2021

The Conference on Retroviruses and Opportunistic Infections (CROI) for 2021 was, as with so many other conferences in the past 12 months, held online. CROI provided a forum for basic scientists and clinical researchers to bring together and discuss their work on human retroviruses and associated diseases, with HIV and SARS-CoV-2 being the two viruses most covered this year. Below are some examples of the work presented at the conference, highlighting both the innovative approaches to understanding and treating viral infections but also the breadth of topics covered

Spatial control of microtubule shrinkage

Microtubules are long linear polymers that switch randomly between periods of growth and shrinkage, in a process known as dynamic instability. In vivo, dynamic instability is regulated by microtubule associated proteins (MAPs). One class of MAPS, the kinesins, move actively along microtubules, and some regulate microtubule dynamics. Kinesin-8, a kinesin, regulates microtubule dynamics in a wide range of eukaryotic cells. Schizosaccharomyces pombe (S. pombe) provides a well-characterised system in which to study microtubule regulation by MAPs. During interphase, microtubules grow from the centre of the rod-shaped cell until their plus ends reach and pause at the cell end, before undergoing catastrophe and shrinking. Shrinkage occurs predominantly at cell ends, even as the cell grows longer. I have studied the cell biology of kinesin-8-dependent interphase microtubule dynamics in S. pombe. I have identified an interphase-specific binding partner of S. pombe kinesin-8 (Klp5/Klp6); Mcp1. Mcp1 was required for Klp5/Klp6 accumulation at interphase microtubule plus ends and for Klp5/Klp6 induced interphase microtubule shrinkage. Tea2 (a kinesin) and Tip1 (CLIP170 orthologue) were found to stabilise interphase microtubules. Cells lacking Tea2 or Tip1 displayed interphase microtubules which, after reaching cell ends, underwent shrinkage sooner than wild type cells. Cells lacking Klp5/Klp6 or Mcp1 showed the opposite phenotype, microtubules which dwelt at cell ends longer than control cells before shrinking. Klp5/Klp6 accumulation on interphase microtubule plus ends steadily increased, peaking just before microtubule shrinkage. In contrast, Tea2 accumulated rapidly to newly nucleated interphase microtubule plus ends and was lost before microtubule shrinkage. I propose a model in which Tea2 prevents Klp5/Klp6 induced microtubule shrinkage until the interphase microtubule has grown to the cell end, where Tea2 is lost. At the cell end Klp5/Klp6 now induce shrinkage

Science For All

Science is the best method humanity has for understanding the universe and our place in it. However, despite its astonishing achievements, the implementation and communication of science is not without problem. In this article the development of scientific publishing is discussed, as is its subsequent impact on scientific discovery and on the profession itself. The ways in which a move towards a more open science framework might alter how science is reported and ultimately performed is also addressed

Role and regulation of kinesin-8 motors through the cell cycle

Members of the kinesin-8 motor family play a central role in controlling microtubule length throughout the eukaryotic cell cycle. Inactivation of kinesin-8 causes defects in cell polarity during interphase and astral and mitotic spindle length, metaphase chromosome alignment, timing of anaphase onset and accuracy of chromosome segregation. Although the biophysical mechanism by which kinesin-8 molecules influence microtubule dynamics has been studied extensively in a variety of species, a consensus view has yet to emerge. One reason for this might be that some members of the kinesin-8 family can associate to other microtubule-associated proteins, cell cycle regulatory proteins and other kinesin family members. In this review we consider how cell cycle specific modification and its association to other regulatory proteins may modulate the function of kinesin-8 to enable it to function as a master regulator of microtubule dynamics

Identification of a Sgo2-Dependent but Mad2-Independent Pathway Controlling Anaphase Onset in Fission Yeast

The onset of anaphase is triggered by activation of the anaphase-promoting complex/cyclosome (APC/C) following silencing of the spindle assembly checkpoint (SAC). APC/C triggers ubiquitination of Securin and Cyclin B, which leads to loss of sister chromatid cohesion and inactivation of Cyclin B/Cdk1, respectively. This promotes relocalization of Aurora B kinase and other components of the chromosome passenger complex (CPC) from centromeres to the spindle midzone. In fission yeast, this is mediated by Clp1 phosphatase-dependent interaction of CPC with Klp9/MKLP2 (kinesin-6). When this interaction is disrupted, kinetochores bi-orient normally, but APC/C activation is delayed via a mechanism that requires Sgo2 and some (Bub1, Mph1/Mps1, and Mad3), but not all (Mad1 and Mad2), components of the SAC and the first, but not second, lysine, glutamic acid, glutamine (KEN) box in Mad3. These data indicate that interaction of CPC with Klp9 terminates a Sgo2-dependent, but Mad2-independent, APC/C-inhibitory pathway that is distinct from the canonical SAC