Category Archives: Biology

Biology

Harnessing Tumor Biology to Improve Outcomes in Advanced … – UroToday

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Alicia Morgans: Hi, I'm so excited to be with Professor Gerhardt Attard of the University College of London, where we're going to be talking about how we really think about using basic biology and our advances in that space to help us understand how to best take care of patients with advanced hormone-sensitive prostate cancer. Thank you so much for being here with me today.

Gerhardt Attard: Thank you for asking me.

Alicia Morgans: Wonderful. So, you do so much work in this space, a lot of translational investigation to help us really pin down more clearly what exactly we're dealing with and what a patient's prognosis might be in this setting. Can you share a little bit about the work that you're focusing on at this point?

Gerhardt Attard: Yeah, so we split it. The question is, how can we use biology to improve our patient outcomes? And we split it in two. The first series of large experiments we've been doing, both my group and the community, is retrieving tumor samples from the several positive phase three trials we've conducted, and then extracting molecular data from those. That gives us information on the underlying biology, what pathways are overactive, what changes are present, other immune infiltrates, etc. And then we test those for associations with outcome. And that can start to tell us which signatures are driving aggressiveness, which signatures are maybe not as relevant in the trajectory of that patient's cancer.

And the second way biology can be used is to identify new targets, and clearly the well-tested path of you taking targets validated in advanced drug-resistant disease and then taking them forward, that's been highly successful. But there are other things we need to be thinking about in terms of better understanding the biology at presentation and then looking for therapeutic opportunities.

Yeah. So broadly, those are the two areas. Now you mentioned prognostic tests, and I think we do need prognostic tests. All patients should now receive a backbone of ADT, so standard androgen deprivation therapy, plus a new-generation hormonal agent. And clearly, that's going to significantly improve outcomes. And in fact, in our recent report from the final data in the STAMPEDE trial, we showed that nearly half of the low-volume patients are in remission at eight years, but there's still a significant proportion, about 30%, who die from prostate cancer. So we need to identify those patients and give additional treatments while sparing the toxicity of further treatment intensification for the patients who are in a good prognostic category. And there's the same for the locally advanced and, to some extent, also for the high-volume metastatic patients.

Alicia Morgans: I want to explore that intensification; we'll get there in a second. But I think that one of the things that the community's been so interested in as well is whether we might be able to not just spare further intensification but even deescalate to the point of using a discrete duration of systemic therapy for our patients with that lower-risk prostate cancer and perhaps even have treatment discontinuation at some point. Do you expect that this might be something that we could hone in on as well as we do this work?

Gerhardt Attard: Yes, potentially. Although I think we have a very good biomarker in PSA and the ADerm of PSA, that gives us an accurate indication of androgen receptor activity, prostate cancer activity. And there are a number of deescalation trials being planned both in the U.S. and in Europe. And those are centered generally around stopping treatment or interrupting treatment when PSA drops below 0.2. Whether we can also integrate upfront molecular data in those sorts of designs, that's up for debate. But in my mind, for those deescalation programs, PSA is offering us, well, it could potentially be a very economical and efficient way.

Alicia Morgans: I guess we will see, but certainly an area to explore as well. So when we think about intensification, and this is an area that you really, of course, are very interested in, what are your strategies, what kind of data have really supported this sort of a direction for our patients?

Gerhardt Attard: So triplet therapy, docetaxel, NHA, ADT, there are a number of trials, PEACE1, which was the French European study, and then ARASENS, both showed survival benefits for adding NHA to a backbone of ADT docetaxel. And clearly, the numerical median survivals with triplet therapy appear longer than NHA plus ADT, but there's a cost to using docetaxel. There's a clear cost in terms of quality of life. There's a study I'm very proud that STAMPEDE produced where we looked at patients who were concurrently randomized either to abiraterone or docetaxel, and as you'd expect there's an initial drop in quality of life at six months with docetaxel, but most notably it doesn't fully recover to the same scores as with abiraterone even 18 to 24 months after treatment. And we didn't meet the pre-specified significance for saying docetaxel scores were less, but they clearly look less. I think that's a big thing for patients.

And the second important point is the effect of docetaxel is heterogeneous. So we see no benefit in high-risk localized, unlike with novel hormonal agents. And there are a number of analyses that have identified differential effects by clinical factors. And I think clinically, at least in advanced drug-resistant disease, we see that as well. So I think we really need a predictive biomarker to make the best of the triplet therapy opportunity. And we're working on that and we're working together with others, especially CHAARTED, the CHAARTED trial with Chris Sweeney because we really need to pool our data sets together to have enough events and enough power, enough robustness, to confidently address the treatment effect questions. So a predictive test is challenging to identify but I agree with you, that should clearly be our primary aim.

Alicia Morgans: Absolutely. I don't think that there is currently as heated a debate as whether or not we should add docetaxel to our treatment algorithm for patients with metastatic hormone-sensitive disease, so if you could help us with the work that you're doing to predict, even in patients who might have low-volume metastatic hormone-sensitive disease who may benefit from docetaxel, this will help all of us and especially our patients, I think, make some proper decisions and better decisions for their future treatment. So as you think about all of this work and where we go from here, where do you want to go next?

Gerhardt Attard: So we are starting a new trial, STAMPEDE2, which will have three randomizations. So that's patients will be randomized to PSMA lutetium or ADT ARASENs alone, so it's triplet therapy, but PSMA lutetium versus doublet NHADT, SABR for the oligo-met, I should say PSMA lutetium we're reserving for those patients who cannot have SABR, either because of the number of METS or the technical challenges of doing that. And all these patients will undergo next-generation sequencing and those that have a BRCA alteration will be randomized to PARP inhibitor with Niraparib plus NHADT versus ADTNHA alone. And the intention over the next few years is to integrate the tests we've been discovering into that platform to prospectively validate them. So we've discussed the prognostic test, the opportunity for predictive tests, but overall we will need prospective trials where we use the test to influence the management of patients. And that's my goal for the next decade, I guess, integrate those tests and prove that we will improve patient outcome by making a decision based on that test.

Alicia Morgans: Well, I really look forward to seeing that in the future and certainly to the quality of life data that I'm sure you'll be collecting with STAMPEDE, it's a wonderful group.

Gerhardt Attard: Which you are part of. So you'll be leading on the quality of life data, so that's excellent.

Alicia Morgans: Very excited that you're including some ex-UK folks in that analysis, and I'm so excited to participate in that work and very grateful that the team from the UK is willing to involve some folks outside of the country. So as you think about this big topic of biology, of advanced hormone-sensitive prostate cancer, where we've been, the work you're doing, and where you want to go, what would your summary be?

Gerhardt Attard: So we have a clear backbone that all patients should receive, ADT novel hormonal agents. On top of that, we have populations that should receive radiotherapy to the primary, there are opportunities for additional treatments such as docetaxel. I think we've made great progress, we're now better understanding the biology and we need to translate that improved understanding into better tests to prognosticate, and then secondly to predict which treatment will work best for a patient.

Alicia Morgans: Wonderful. Well, thank you so much for sharing all of this with us today. We appreciate your time and expertise.

Gerhardt Attard: Thank you.

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Harnessing Tumor Biology to Improve Outcomes in Advanced ... - UroToday

Biology

Improving Tumor Microenvironment Proteomics Using Spatial Biology – The Scientist

This webinar will be hosted live and available on-demand

Wednesday, December 6, 2023 11:00 AM Eastern Time

Immunohistochemistry and flow cytometry are valuable laboratory tools for analyzing cells but are limited for applications that require access to high resolution, high-plex spatial information and complex datasets simultaneously. For example, scientists require detailed information about the spatial distribution of key immune cell populations in order to advance their understanding of human disease and inform the development of novel therapeutics.

In this webinar brought to you by Canopy Biosciences A Bruker Company, Thomas Campbell will present CellScape, a novel image-based platform that uses ChipCytometry technology for high-plex quantitative, single-cell spatial proteomics.

Topics to be covered

Thomas Campbell, PhD Associate Director of Product Management Canopy Biosciences

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Improving Tumor Microenvironment Proteomics Using Spatial Biology - The Scientist

Biology

Applications of Time-Resolved Spectroscopy in Biology – AZoOptics

Time-resolved spectroscopy (TRS) is a powerful analytical technique that has found its way into various scientific disciplines. Among these, biology has emerged as a promising domain where time-resolved spectroscopy offers valuable insights into complex biological processes. This article discusses time-resolved spectroscopy in biology, providing a comprehensive understanding of its significance, recent trends, technical details, and recent studies.

Image Credit:Gorodenkoff/Shutterstock.com

In biology, many vital processes happen in milliseconds, microseconds, or even femtoseconds. Time-resolved spectroscopy can capture these fleeting moments with incredible precision. For instance, it can reveal the kinetics of enzymatic reactions, electron transfer in photosynthesis, or protein folding - all in real-time.

Moreover, Time-resolved spectroscopy is not limited to monitoring kinetics alone but also unveils structural changes within biomolecules. This is particularly important in studying protein conformational changes, which play a crucial role in various diseases. Time-resolved spectroscopy can also detect changes in pH, ion concentration, and temperature, offering insights into how these factors affect biochemical reactions. Another crucial advantage of Time-resolved spectroscopy is in drug development and disease studies since it helps understand how drugs interact with their target molecules in real-time. For instance, it has applications in cancer research, where it can monitor the dynamics of cell proliferation and migration.

Recent developments have seen the integration of various spectroscopic techniques with Time-resolved spectroscopy, allowing for a more comprehensive understanding of biological processes. Combining Time-resolved spectroscopy with other methods like NMR, X-ray crystallography, and electron microscopy provides a multi-dimensional view of complex biological systems.

Similarly, single-molecule Time-resolved spectroscopy has gained momentum, enabling researchers to monitor individual molecules and observe their behavior in great detail, especially in studying biomolecular interactions and conformational changes.

Another emerging trend is combining Super-resolution microscopy with Time-resolved spectroscopy to achieve spatial resolutions far beyond the diffraction limit. This has opened new horizons in studying subcellular structures and cellular processes, allowing researchers to visualize the previously unseen.

Recent trends are leaning towards in vivo applications of Time-resolved spectroscopy as well. This involves the non-invasive monitoring of biological processes within living organisms, making it a potential game-changer in fields like neuroscience, pharmacology, and medical diagnostics.

Time-resolved spectroscopy relies on the interaction between matter and electromagnetic radiation. Pluses of light as brief as femtoseconds are generated in the form of ultra-short laser pulses, allowing the capture of ultrafast events. A laser pulse is directed at the biological sample, which interacts with the sample, inducing changes that affect the properties of the probing light, such as its wavelength, polarization, or intensity.

A second pulse of light, often referred to as the probe pulse, is used to measure the changes in the properties of the initial pulse. The time delay between the pump (excitation) and probe pulses is precisely controlled. Hence, the data collected is analyzed to reconstruct the temporal evolution of the sample's properties, providing insights into the dynamic processes taking place in the biological system.

In a 2021 study, researchers explored the applications of Time-resolved spectroscopy in the field of biology, focusing on optogenetic channels, specifically channelrhodopsins (ChRs) and anion channelrhodopsins (ACRs). They investigated the photocycle of the natural ACR, Guillardia theta Anion Channelrhodopsin-1(GtACR1), and compared it with the well-studied ChR (Chlamydomonas reinhardtii Channelrhodopsin-2), CrChR2. These are specific types of proteins or channelrhodopsins. They conducted time-resolved UV/VIS and FTIR spectroscopy to monitor the dynamic molecular processes during the photocycle of GtACR1.

The study revealed the absence of a light-adapted state in GtACR1, distinguishing it from CrChR2. GtACR1 demonstrated higher peak currents and reduced inactivation, which are attributed to its preexisting tunnel and the absence of a syn-photocycle. The research provided insights into the molecular mechanisms of GtACR1's channel gating and its differences from CrChR2, enhancing the understanding of optogenetic tools' design and applications in biology.

The future prospects of Time-resolved spectroscopy in biology are exceptionally promising. Time-resolved spectroscopy is poised to revolutionize the study of complex biological processes, offering invaluable insights and applications. As technology advances and research in this field evolves, several exciting developments can be anticipated, including enhanced multimodal integration, as Time-resolved spectroscopy combines with other advanced spectroscopic techniques like NMR, X-ray crystallography, and electron microscopy. This integration will provide a more comprehensive understanding of complex biological systems.

Similarly, the shift towards in vivo applications involving non-invasive monitoring of biological processes within living organisms holds immense potential in fields such as neuroscience, pharmacology, and medical diagnostics. These advancements will collectively shape and enhance our understanding of biological processes, offering new avenues for research and applications in biology.

More from AZoOptics: Raman Spectroscopy for Label-Free Chemical Analysis

Dreier, M. A., Althoff, P., Norahan, M. J., Tennigkeit, S. A., El-Mashtoly, S. F., Lbben, M., ... & Gerwert, K. (2021). Time-resolved spectroscopic and electrophysiological data reveal insights in the gating mechanism of anion channelrhodopsin. Communications Biology. https://doi.org/10.1038/s42003-021-02101-5

Schmitt, M., Dietzek, B., Hermann, G., & Popp, J. (2007). Femtosecond timeresolved spectroscopy on biological photoreceptor chromophores. Laser & Photonics Reviews. https://doi.org/10.1002/lpor.200710005

Gupta, B. K., Rathee, V., Narayanan, T. N., Thanikaivelan, P., Saha, A., Govind, ... & Ajayan, P. M. (2011). Probing a Bifunctional Luminomagnetic Nanophosphor for Biological Applications: a Photoluminescence and TimeResolved Spectroscopic Study. https://doi.org/10.1002/smll.201100441

Masuch, R., & Moss, D. A. (2003). Stopped flow apparatus for time-resolved Fourier transform infrared difference spectroscopy of biological macromolecules in 1H2O. Applied spectroscopy. https://doi.org/10.1366/000370203322554581

Disclaimer: The views expressed here are those of the author expressed in their private capacity and do not necessarily represent the views of AZoM.com Limited T/A AZoNetwork the owner and operator of this website. This disclaimer forms part of the Terms and conditions of use of this website.

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Applications of Time-Resolved Spectroscopy in Biology - AZoOptics

Biology

Why genes mean less than you think, and other reads: Books in brief – Nature.com

The Master Builder

Alfonso Martinez Arias Basic (2023)

The structure of DNA was discovered in Cambridge, UK, in 1953. How ironic, then, that it was while he was a researcher in the department of genetics at the University of Cambridge that biologist Alfonso Martinez Arias developed doubts that genes constitute an organisms operating manual. For example, he says, genes cannot explain why the human heart is usually on the left or why the hand has five fingers. In his revolutionary book on cell biology, he argues: I feel certain that cells hold a creative potential that genes cannot dream of.

Igor Tulchinsky & Christopher E. Mason MIT Press (2023)

Chief executive of a quantitative-investment firm Igor Tulchinsky, and Christopher Mason, who runs a genomic medicine laboratory, share an interest in prediction. Predictive algorithms have changed the world, and all the worlds to come, and there is no going back, they say in their articulate book on how current and future artificial-intelligence algorithms will change apprehension of risk and affect human behaviour. They accept that economics, business, finance and some aspects of medicine are not governed by scientific logic.

Caleb Everett Harvard Univ. Press (2023)

In the Amazonian region of Brazil, where anthropologist Caleb Everett spent much of his childhood, speakers of Tupi-Kawahb never refer to time passing by. Indeed, the language has no word for time. By contrast, most European languages have few abstract words for odours, whereas languages in a number of other cultures have more than a dozen. Everetts fascinating book based on collaboration with biologists, chemists, political scientists and engineers ponders such differences between the worlds 7,000-plus languages.

Paul Mattick Reaktion (2023)

According to Paul Mattick, former editor of the International Journal of Political Economy, who trained in philosophy, economists have a long record of theoretical and predictive failure. After failing to predict the 2008 financial crisis, they failed to explain why inflation stayed unexpectedly low for a decade, before suddenly rising in 2021. Was the COVID-19 pandemic responsible for the high inflation? If so, why does it continue? This book, from a left-wing perspective, argues that modern capitalism is inherently inflationary.

Graeme Blair et al. Princeton Univ. Press (2023)

This is a research design book, not a statistics textbook, note political scientists Graeme Blair, Alexander Coppock and Macartan Humphreys. It is aimed at readers launching their first research projects in the social sciences, at graduate students wishing to understand research findings and at funders assessing a projects design rather than its results. Its unique framework, MIDA (model, inquiry, data strategy and answer strategy), uses DeclareDesign, a software package co-created by the authors.

The author declares no competing interests.

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Why genes mean less than you think, and other reads: Books in brief - Nature.com

Biology

‘They thought we were nuts.’ Rocky Mountain BioAg puts the biology … – Montrose Daily Press

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'They thought we were nuts.' Rocky Mountain BioAg puts the biology ... - Montrose Daily Press

Biology

Why we have better maps of Mars than of the seafloorand what … – United States Geological Survey (.gov)

Compared to the terrestrial surfaces of our own planet, or even those that are millions of miles away in the solar system, we know so little about the topography of the seafloor that new discoveries of massive features like seamountssuch as this one off the coast of Californiacontinue to be made today.

At the root of this is a problem of technology. The tools we use to image land above water rely on sending and recording wavelengths of light through methods such as satellite imaging or LiDAR. These can produce highly accurate and detailed pictures of the surface of the earth in a matter of days.

But light does not penetrate through seawater beyond the first few hundred feet. With the maximum depth of the ocean plunging to more than 36,000 feet, we need alternative methods for surveying the seafloor.

While light is rapidly attenuated in seawater, sound can travel for thousands of miles. Seafloor mapping technology relies on sonar devices

mounted either to the hull of a ship or on remotely operated and autonomous underwater vehicles. These devices emit pulses of sound in a fan shape across the seafloor, measuring the time it takes for the sound to travel and reflect off the seafloor, then return to the ship. With as many as 60 pulses of sound per second, the swath of the sonar survey can collect millions of data points of water depth as the ship travels.

Computer software transforms these data into a visual image of the seafloor. In November 2023, scientists from the USGS sailed approximately 350 miles from Honolulu, Hawaii, to explore a little-surveyed, crescent-shaped area of the seafloor south of the Hawaiian Islands. Working in partnership with BOEM and the NOAA Ocean Exploration Cooperative Institute, the USGS conducted bathymetric surveys and environmental DNA sampling aboard the ten-day expedition. This is the first time this partnership has investigated and characterized the seafloor geology and biology of the Hawaiian abyssal plain.

The deeper the seafloor, the more challenging it is to obtain a high-resolution map, because the sound must travel farther. Abyssal plains are often neglected in mapping efforts since they are deeper than the average depth of the seafloor and therefore challenging to map; they also generally have less charismatic fauna than shallower seamounts. Further, mapping efforts often focus on resolving features that can be seen through low-resolution satellite imagery, and at this resolution abyssal plains appear flat and featureless. However, abyssal plains are the largest ocean floor environment, and their sediments preserve the history of oceanic processes and support crucial biogeochemical processes, including carbon sequestration.

Bathymetric surveys allow us to understand not only the ocean depths and the shape of the seafloor (is it flat or steeply sloping?) but also tells us about its composition (is the surface texture hard or soft?) based on the relative intensity of the sound reflection. This information is crucially important because the shape and composition of the seafloor affects the physical and biological processes within the ocean. Bathymetric maps are the foundation for deep-sea exploratory missions aiming to understand regional biology, geology, and chemistry, and serve as important tools for defining marine protected areas.

Much in the way that a house with stairs as opposed to ramps to walk up and downor soft, plush carpet versus hardwood floorswould affect your comfort and mobility in your home ecosystem, the dynamic topography and structure of the seafloor shapes the types of ecosystems found on the seafloor. The sharp vertical relief offered by submarine canyons and continental shelves is also what drives ocean currents that cycle vital nutrients and oxygen to sustain marine food webs.

As the nations lead scientific mapping agency, the USGS brings a wealth of expertise in the interpretation of bathymetric survey data to understand the shape and geologic structure of the seafloor. Accurate, modern, high-resolution bathymetric maps are essential for delineating and protecting sensitive marine habitats, guiding the wise use of marine resources, ensuring safe maritime navigation, and detecting seafloor geologic hazards that can threaten coastal populations and infrastructure.

Because of the importance of this information and the existing data gaps, the U.S. is supporting global advancements in ocean mapping through a consortium of federal agencies forming the National Ocean Mapping, Exploration, and Characterization Council (NOMEC). As co-chair of the NOMEC council, the USGS helps lead the charge in coordinating and implementing collaborative mapping, exploring, and characterization of the nations ocean waters. With this Hawaiian expedition, the USGS contributes to mapping the gaps in U.S. waters and provides insight into this understudied ecosystem by characterizing its deep-sea biology and geology.

Strategic partnerships developed with other federal agencies such as BOEM and NOAA, as well as with private and academic collaborators such as the Scripps Institution of Oceanography, Schmidt Ocean Institute, and Ocean Exploration Trust, have greatly expanded mapping and exploration of hazards and deep-sea ecosystems off the west coast of the United States.

The USGS has a unique role and mission as the federal provider of research expertise on marine geology, geophysics, and the processes that form and alter seabed and sub-bottom environments. USGS capacities in marine geology, geologic and oceanographic processes, and marine biology, ecology and geochemistry are all essential to NOMEC goals to map and characterize marine hazard and resource potential, seabed ecosystems, and the consequences of human and natural change.

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Why we have better maps of Mars than of the seafloorand what ... - United States Geological Survey (.gov)

Biology

Yurok biologist has whirlwind couple of weeks | Community … – The Triplicate

Its been a busy couple of weeks for Yurok tribal citizen and Senior Fisheries Biologist for the Yurok Tribe of California Keith Parker.

He sat in his living room talking with a New York Times reporter answering questions and addressing issues pertinent to Northern California and fish management on the Klamath River.

He spent time out on the river with the Times photographer as the team put together a presentation that will run not only in the New York City daily, but another piece entitled The scientists watching their lifes work disappear, will run in the New York Times Sunday Magazine with a circulation of 6 million readers.

Then on Oct. 19-21, at the 2023 American Indian Science Engineering Society National Conference (AISES) in Spokane, Wash., he and the largest audience in conference history (3,500) watched a five-minute video of his work.

AISES is a national nonprofit organization focused on increasing representation of Indigenous peoples of North America and the Pacific Islands in science, technology, engineering, and math (STEM) studies and careers.

Senior Fisheries Biologist for the Yurok Tribe of California Keith Parker out on the Klamath River.

Parker was recognized as the AISES 2023 Professional of the Year for Technical Excellence.

It was a record turnout at Spokane, so that was special. Its been a lot of hard work, said Parker, a molecular biologist who helps monitor the Klamath Rivers fish stocks as part of the Klamath River Technical Team.

The New York Times article came out. Then in a separate article that just came out digitally, they did another article talking about scientists that are hoping to help fix climate change for their Sunday magazine. So, its been a hell of a week.

Growing up, Parker bore witness his grandfather leading protests of federal bans on tribal fishing rights, ironically, for water he is now responsible for, co-stewarding the Klamath Rivers 44 miles through the Yurok reservation.

His research has been published in the science journal, Molecular Ecology. In 2018, he discovered two new previously undiscovered subspecies of Pacific lamprey a jawless fish that looks like an eel one that matures in the river and another that matures in the ocean.

I used Yurok words to describe them because of the importance they are for our people. Kewsween means river, and the ocean maturing lamprey was named Tewol, which is the Yurok word for ocean, he explained. The lamprey has great cultural and historical value to Pacific Northwest tribes.

He has also performed a great deal of genetics work on the Klamath salmon in collaboration with the University of California-Santa Cruz.

All that aside, having the New York Times reporter and photographer sitting in his living room while his son Beau shot some photos of the process is a memory they will share for a long, long time, he said.

I was humbled and at the same times excited, because every time these things happen, it gets the word out to more people about the plight of our salmon and our fisheries here on the West Coast, specifically Del Norte County, said Parker, who co-stewards harvest management on the lower 44-miles of the Klamath River eight-months of the year and conducts genetic analysis of returning Trinity River Hatchery salmon in collaboration with UC Santa Cruz the rest of the time

We had a full salmon closure this year in the ocean and the river. They shut down the rock fishing season, so all the local fishermen cant fish the shores. We have a lot of fishery issues because of degraded rivers and poor ocean conditions. So, if I can get in front of that many people (through the New York Times), then I can educate more people about these problems. Hopefully, more people are going to be thinking about solutions.

Parker, who also has family in the Karuk, Hupa and Tolowa communities, is a regular guest speaker, discussing climate change and drought on salmon populations.

He has conducted numerous fisheries biology, hydrology, and river ecology research projects in Alaska, Washington, Idaho and California. He received a BS degree in Fisheries Biology (2015) and a MS degree in Natural Resources (2018) from Cal Poly-Humboldt, with a thesis on conservation genetics.

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Yurok biologist has whirlwind couple of weeks | Community ... - The Triplicate