Spotlight on Cell Biology: Cell biology takes the stage
ASCB|EMBO annual meeting goes virtual this year with cellular research. Two of the most significant changes aside from the online format are that the meeting will feature seven scientific tracks plus an education and professional development track, in addition to member-organized Special Interest Subgroups being held on three days of the meeting.
The American Society for Cell Biology (ASCB) and the European Molecular Biology Organization (EMBO) have taken their ASCB|EMBO meeting to an online format this year, launching Cell Bio Virtual 2020, which will take place Dec. 2-16.
As the organizers note, “Exciting features are planned for Cell Bio Virtual 2020 ... Diversity and inclusivity are extremely important to our organization and members, and we strive to reflect this within our meeting. In light of the COVID-19 pandemic, we are offering the same great content in an online format where you can participate in the meeting from your own location.”
Two of the most significant changes aside from the online format are that the meeting will feature seven scientific tracks plus an education and professional development track, in addition to member-organized Special Interest Subgroups being held on three days of the meeting.
“Cell Bio is an arena to showcase the brightest minds in the cell biology community,” the organizers explain. “Our community encompasses researchers from diverse backgrounds, including age, gender, race, ethnicity, geographic location, institutions, career levels and research interests.”
The keynote lecture is titled “Archaic Genomics” and will be presented by Svante Pääbo, director of the Max Planck Institute of Evolutionary Anthropology in Germany, who is also part of the Okinawa Institute of Science and Technology in Japan. Pääbo and his team developed a technique of isolating and sequencing the DNA of creatures long extinct using a variety of fragile, ancient source material from Homo sapiens and other human species.
Other highlights include the symposia “Cells in Distress and Disease,” “Dynamic Intracellular Organization,” “Cell Shape, Cell Division, Migration and Death,” “Growth, Pattern and Form,” “Information Processing,” “Cellular Identity,” “How Different Cells Interact: Sex, War, Competition,” “Collective Cell Behavior” and “The Genome.”
Mini-symposia, roundtable discussions, professional development programming and more will also be on tap, as with the physical meetings in the past. For more information, visit the official website at www.ascb.org/cellbiovirtual2020.
But we have more to share about cell biology research beyond Cell Bio Virtual, so keep reading to see some of the more exciting elements of what’s happening right now in the field.
Investigating host tolerance to genes that jump
An evolutionary geneticist at the University of Houston recently received a $1.8-million grant to investigate “parasites” that jump onto reproductive cells. As the university puts it, “Within your genome ... 50 percent is composed of transposable elements. [That] means you are 50-percent parasite. Odder still, the parasites tend to jump onto sperm and egg cells in their driving need to replicate to the next generation, thus earning the nickname 'jumping genes.'”
For some egg or sperm cells, that invasion is devastating, causing strands of DNA to either break or shatter and leading to an inability to produce healthy reproductive cells. For other, more genetically tolerant gametes, the jumping gene may not break them, but may cause the offspring to be born with genetic disorders.
“We’re trying to determine how a developing gamete might be able to persist despite this damage from the jumping genes,” said Dr. Erin Kelleher, associate professor of biology and biochemistry at the University of Houston. Interestingly, surviving in the face of invasion is also what tumors do, as jumping genes cause chaos and mutations in them.
"Transposable element activity is implicated in the onset and progression of many tumor types and age-related neurodegenerative diseases,” Kelleher explained. “Understanding how specific genetic variants of bruno provide tolerance to developing fruit fly eggs may point to similar mechanisms in tumor cells."
Kelleher previously published findings on how the bruno gene, which regulates development of the egg, influences tolerance in the fruit fly genetic model Drosophila melanogaster. By studying fruit flies collected in the past and comparing them to contemporary fruit flies, Kelleher is asking whether tolerant individuals have become more common through natural selection.
She will combine genetic analysis of mutant gene formations (alleles) with bruno variants isolated from Drosphila populations to reveal the underlying mechanism and recent evolutionary history of bruno-dependent tolerance.
Identifying T cell epitopes presented by SARS-CoV-2-infected cells
Meanwhile, on the topic of COVID-19, the very pandemic that pushed the ASCB|EMBO meeting online, Emergex Vaccines Holding Ltd. and George Mason University (GMU) have presented what is said to be the first detailed, empirical analysis of class 1 epitopes presented by SARS-CoV-2-infected cells.
During the collaboration, researchers at GMU grew SARS-CoV-2, the virus which causes COVID-19, in human cells expressing ACE-2 that represent six human leukocyte antigen supertypes to create an MHC class I peptide expression library. In doing so, they have defined the T cell repertoire necessary for CD8+ cytotoxic T cells to perform their “kill-and-clear” function of an infected cell. Details of the library have potentially significant implications for the development of T cell-targeted COVID-19 vaccines and also T cell memory diagnostic reagents that can definitively determine the pre-exposure history of COVID-19.
Emergex will apply the insight gained in this study in its ongoing program to generate a second-generation COVID-19 vaccine, which is intended to generate a lasting and safe cellular immune response.
“It is increasingly clear that T cell responses to SARS-CoV-2 are the major—if not dominant—factor in the immune response to COVID-19 infection and a vaccine which can safely and effectively harness this response could be critical to controlling the pandemic,” said Prof. Thomas Rademacher, CEO and co-founder of Emergex.
Added Dr. Aarthi Narayanan, an associate professor of systems biology at GMU: "This is an exciting and highly pertinent approach to develop a vaccine against SARS-CoV-2 which takes into account the critical need for a robust and targeted T-Cell response to elicit functional immunity."
Implicating a new gene in neuron diseases
Failures in a quality control system that protects protein-building fidelity in cells can lead to motor neuron degeneration and related diseases, according to a new study from an international team co-directed by Scripps Research molecular biologist Dr. Claudio Joazeiro.
Motor neurons control movement, breathing, swallowing and speaking. Their death is a hallmark of progressive diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease. Understanding what can cause motor neurons to die is key to developing precision treatments.
The study, appearing in the journal Nature Communications, singles out several variants of a gene called NEMF as new drivers of motor neuron diseases. NEMF, short for “nuclear export mediator factor,” is known for its role in helping clear glitches that inevitably occur during protein production by cellular organelles called ribosomes.
Healthy NEMF helps the cell recycle garbled protein fragments produced in error. But several mutant forms of NEMF in mice interfered with the system and resulted in neuromuscular, neurodegenerative or other disease, the scientists found.
The research was led by both Joazeiro—who has joint appointments at Scripps Research in Jupiter, Fla., and the Center for Molecular Biology of Heidelberg University in Germany—and Dr. Gregory Cox of the Jackson Laboratory of Mammalian Genetics in Bar Harbor, Maine.
A decade ago, Joazeiro discovered an enzyme, the E3 ubiquitin ligase listerin/Ltn1, that works in a specialized quality control process now known as RQC, or ribosome-associated quality control. He and his team also found that inactivation of the enzyme causes motor neuron degeneration in mice. However, whether neurodegeneration resulted from defective ribosome-associated quality control or some other function of listerin remained unclear.
At the Jackson Laboratory, Cox had been studying mice with mutations in another quality control factor: NEMF. They exhibited movement difficulties, including walking and gripping. The labs teamed up to investigate whether those defects resulted from a neurodegenerative process. They wanted to find the molecular mechanisms at work.
“The results provide strong evidence that dysfunction of ribosomal quality control causes neurodegeneration,” Joazeiro commented.
The team is now investigating the role of ribosome-associated quality control in other related diseases.
Another takeaway from this research is that this pathway of protein quality control appears to be necessary across species, Joazeiro says, adding, “Last year we reported that it is also present in bacteria, and is likely to have already been active in the last universal common ancestor, the organism that gave rise to all domains of life.”
Together with the findings that disabling the system results in neurodegeneration, this evolutionary conservation highlights the importance of aberrant protein disposal, and also suggests the system’s development may have played a critical role enabling the evolution of complex organisms, he noted.
