Scientific Seminars

Zoom link: https://hhmi.zoom.us/j/95859517201?pwd=b2pha2xhWWk4a1BteWJrcStVUWdOQT09

Moderator: Asya Rolls, Associate Professor, Technion, Israel

Speakers:

Michal Schwartz, Professor, Weizmann Institute, Israel
Adam Kepecs, Professor, Washington University School of Medicine, US
Carlos Ribeiro, Principal Investigator, Champalimaud Neuroscience Programme, Portugal

More information: https://lifescienceacrosstheglobe.org/

Abstract;
Salmonella enterica is a common foodborne, facultative intracellular enteropathogen. Typhoidal S. enterica serovars like Paratyphi A (SPA) are human-restricted, and cause severe systemic diseases, while many S. enterica serovars like Typhimurium (STM) have a broad host range and in human hosts usually lead to self-limiting gastroenteritis. There are key differences between typhoidal (TS) and non-typhoidal (NTS) Salmonella in pathogenesis, but research on TS is challenging due to host restriction. Since STM causes a typhoid-like disease in mice, it was widely used as model organism to mimic human TS infection. Although results gained by research on STM could provide major insights in Salmonella virulence in general, the specific virulence mechanisms of TS are far from being understood. We recently described the intracellular transcriptomic architecture and phenotypes of STM and SPA during presence in epithelial cells. Surprisingly, Salmonella pathogenicity island 1 (SPI- 1) as well as motility and chemotaxis genes showed distinct expression patterns in intracellular SPA vs. STM. We observed that induction of flagella genes by intracellular SPA led to cytosolic motility. We report flagella-dependent cytosolic motility of SPA that neither depends on SPI-2 nor on recruitment of host cell actin. The elevated expression of SPI-1 genes resulted in increased invasiveness of SPA, following exit from host cells.The triggers and cellular consequences of cytosolic motility are currently under investigation. Live cell imaging (LCI) revealed that SPA invades host cells in a cooperative manner with multiple bacteria per invasion site, possibly leading to error-prone macropinocytosis with increased membrane damage in the early Salmonella-containing vacuole. After release into the cytosol, motile bacteria showed reduced decoration with autophagosomal protein LC3 in LCI and ultrastructural analyses.Our results provide new insights into the virulence profile of SPA by unravelling previously unknown intracellular phenotypes and virulence traits. We propose cytosolic motility as possible xenophagy evasion mechanism and higher invasiveness as contribution to progression of infection and systemic dissemination in the host. Furthermore, we established 3D and 2D intestinal organoid models which offer new tools for analyses of human-restricted pathogens in a more in vivo relevant context

Zoom link: https://mrc-lmb-cam-ac-uk.zoom.us/j/96648790745?pwd=Tkx6OVpoY01ieTRMTFMzZ0QvWWR2UT09

Twitter handles: @intein @mpimoph

Muscles underpin movement and heart function. Individual muscle fibers can be very large syncytia of up to several centimeters in length and are comprised of the force-generating and load-bearing devices of muscles called sarcomeres. Contraction and relaxation of sarcomeres relies on the sliding between two types of filaments - the thin filament (comprising mainly F-actin, tropomyosin, and troponin) and the thick myosin
filament. In addition, several other proteins are involved in the contraction mechanism and their mutational malfunction can lead to debilitating and even life-threatening diseases. In my presentation, I will explain how we managed to obtain high-resolution structures of native sarcomeres using cryo-electron tomography (cryo-ET). Our cryo-ET reconstructions reveal molecular details of the three-dimensional organization and
interaction of actin and myosin in the A-band, I-band and Z-disc and demonstrate that α-actinin cross-links antiparallel actin filaments by forming doublets with 6 nm spacing. Structures of myosin, tropomyosin, actin, and nebulin at up to 4.5 Å further reveal two conformations of “double-headed” myosin, where the flexible orientation of
the lever arm and light chains enable myosin not only to interact with the same actin filament, but also to split between two actin filaments. The structures provide high-resolution details of the interaction between nebulin and actin, demonstrating the stabilising role of nebulin. Unexpectedly, nebulin does not interact with myosin or tropomyosin, but with a troponin-T linker through two potential binding motifs on nebulin, explaining its regulatory role. Our results provide unexpected insights into the
fundamental organization of vertebrate skeletal muscle and serve as a strong foundation for future investigations of muscle diseases

Microbial rhodopsins form a family of photoreceptive membrane proteins in unicellular microbes. In the 20th century, microbial rhodopsins were considered to have a limited range in species such as hyperhalophilic archaea. However, recent genomic and environmental metagenomic analyses identified many thousands of microbial rhodopsins from diverse microorganisms, such as bacteria, archaea, algae, fungi, and even giant viruses, which use sunlight energy for various biological events.
We studied the molecular functional mechanisms of various microbial rhodopsins by time-resolved laser spectroscopy and vibrational spectroscopy to reveal their structure-function correlation. All microbial rhodopsins have the common chromophore, all-trans retinal, which isomerizes to 13-cis upon illumination. Our spectroscopic studies revealed that the protein moiety of each rhodopsin shows different structural changes in response to retinal isomerization, which leads to different biological function.
We also found many rhodopsin genes having widely different amino acid sequences compared with previously reported ones. As a result, light-driven outward Na+ pump and inward H+ pump microbial rhodopsins were newly identified, and their transport mechanism was also revealed. In 2018, a new distinct class of rhodopsin was discovered by functional metagenomics, and it was named heliorhodopsin (HeR) meaning “the rhodopsin of the sun” in Greek. HeR has an orientation in membrane in which N- and C-termini face cytoplasmic and extracellular side, respectively. This is the opposite to all classical microbial rhodopsins. Furthermore, bestrhodopsin, which is a natural fusion protein between 1 or 2 microbial rhodopsins and bestrophin, forms a gigantic 700 kDa pentameric complex, also found in marine algae in 2022. Bestrhodopsin transports ions through the central pore of the bestrophin domain and it is regulated by the rhodopsin domains in a light dependent manner. The variety of rhodopsins is expected to continue to expand, and many new insights about the essence of protein functionality will be obtained by studying them.

Zoom Link: https://mrc-lmb-cam-ac-uk.zoom.us/j/91021060396?pwd=c1o1TWVTSTNHTWM1dW5lcm54cURKQT09

Social interactions are essential for animals to survive, reproduce, raise their young. Over the years, my lab has attempted to decipher the unique characteristics of social recognition: what are the unique cues that trigger distinct social behaviors, what is the nature and identity of social behavior circuits, how is the function of these circuits different in males and females and how are they modulated by the animal physiological status? In this lecture, I will describe our recent progress in understanding how the brain participates in the positive and negative control of adult-adult social interactions, providing a new framework to understand the regulation of social behaviors in health and disease. Finally, I will describe our recent work uncovering how specific brain circuits are able to direct adaptive changes in behavior during sickness episodes in mice

Zoom link: https://mrc-lmb-cam-ac-uk.zoom.us/j/99349389275?pwd=ZHI3em1DQTA0VTlVLzkvUTN6ZGkxdz09

A hybrid event: in person and online.

Online registration - https://mrc-lmb-cam-ac-uk.zoom.us/webinar/register/WN_joGV-7WaRBW-QM4adVn8fw
In person registration - https://womenatlmb2022.eventbrite.co.uk/

Programme:
10:00 – 11:00 Arrival and coffee

11:00 Introduction Mariann Bienz
11:10 Daniela Rhodes
11:25 Patrycja Kozik
11:40 Pippa Marrack
11:55 Margaret (Scottie) Robinson

12:10 – 14:00 Lunch

14:00 Joan Steitz
14:15 Marta Zlatic
14:30 Gillian Griffiths
14:45 Susan Taylor

15:00 Tea break

16:00 Julie Ahringer
16:15 Lori Passmore
16:30 Elizabeth Blackburn (online)
16:45 Poster session with drinks in LMB atrium followed by buffet in the Restaurant

The Symposium will celebrate the women scientists who work or have worked at the LMB, many of whom have gone on to careers at some of the world's foremost scientific institutions. Many of the women featured in Kathy Weston's book "Ahead of the Curve" (https://aheadofthecurve.org.uk/) will be speaking about their career to date, including how the LMB influenced them. There will be plenty of opportunity for networking with the speakers, current LMB members and other LMB alumnae during this 2 day Symposium

For more information, please visit - https://www3.mrc-lmb.cam.ac.uk/sites/lmbwomensymposium/

A hybrid event: in person and online.

Online registration - https://mrc-lmb-cam-ac-uk.zoom.us/webinar/register/WN_joGV-7WaRBW-QM4adVn8fw
In person registration - https://womenatlmb2022.eventbrite.co.uk/

Programme:
9:00 – 10:00 Arrival and coffee

10:00 Suzanne Cory (online)
10:15 Anne Bertolotti
10:30 Laura Machesky

10:45 Coffee

11:30 Sarah Teichmann
11:45 Madeline Lancaster
12:00 Maria Leptin
12:15 Melina Schuh

12:30 – 14.00 Lunch

14:00 Barbara Meyer (online)
14:15 Kelly Nguyen
14:30 Cynthia Kenyon

14:45 Tea break

15:30 Panel discussion chaired by Maria Leptin with Ruth Sperling, Liz Miller and Yanlan Mao
17:00 Closing remarks Jan Löwe

The Symposium will celebrate the women scientists who work or have worked at the LMB, many of whom have gone on to careers at some of the world's foremost scientific institutions. Many of the women featured in Kathy Weston's book "Ahead of the Curve" (https://aheadofthecurve.org.uk/) will be speaking about their career to date, including how the LMB influenced them. There will be plenty of opportunity for networking with the speakers, current LMB members and other LMB alumnae during this 2 day Symposium

For more information, please visit - https://www3.mrc-lmb.cam.ac.uk/sites/lmbwomensymposium/

Mitochondria fulfil central functions in bioenergetics, cellular metabolism and signalling. The lecture will address how mitochondria import about 1,000 different proteins from the cytosol via specific membrane-bound preprotein translocases, how the proteins are sorted to their correct intramitochondrial location, and how protein transport is connected to the characteristic membrane architecture of mitochondria. Protein translocases do not function as independent units, but are integrated into a network of machineries that function in bioenergetics, metabolism, membrane morphology and formation of organelle contact sites, indicating a higher level organization of cell organelles.

A Reception will be held in the Foyer at 5.00 pm

Further information is available on the Unit’s website: http://www.mrc-mbu.cam.ac.uk. Enquiries to Penny Peck (01223) 252703

Zoom link - https://mrc-lmb-cam-ac-uk.zoom.us/j/94050407947?pwd=ZFZZYkxhd0JsbGJuMFNHQnlzOSsydz09