̽��ֱ�� of Cambridge - ̽��ֱ�� of Pennsylvania

New findings that map the universe’s cosmic growth support Einstein’s theory of gravity

sc604 — Tue, 11 Apr 2023 14:00:00 +0000

̽��ֱ��findings, from the Atacama Cosmology Telescope collaboration involving researchers from the ̽��ֱ�� of Cambridge, provide further support to Einstein’s theory of general relativity, which has been the foundation of the standard model of cosmology for more than a century. ̽��ֱ��results offer new methods to demystify dark matter, the unseen mass thought to account for 85% of the matter in the universe.

For millennia, humans have been fascinated by the mysteries of the cosmos. From ancient civilisations such as the Babylonians, Greeks, and Egyptians to modern-day astronomers, the allure of the starry sky has inspired countless quests to unravel the secrets of the universe.

And although models that explain the cosmos have existed for centuries, the field of cosmology, where scientists use quantitative methods to understand the evolution and structure of the universe, is relatively new—having only formed in the early 20th century with the development of Albert Einstein’s theory of general relativity.

Now, a set of papers submitted to ̽��ֱ��Astrophysical Journal by researchers from the Atacama Cosmology Telescope (ACT) collaboration has produced a new image that reveals the most detailed map of matter distributed across a quarter of the entire sky, reaching deep into the cosmos. It confirms Einstein’s theory about how massive structures grow and bend light, with a test that spans the entire age of the universe.

“We have mapped the invisible dark matter across the sky to the largest distances, and clearly see features of this invisible world that are hundreds of millions of light-years across,” said co-author Professor Blake Sherwin from Cambridge’s Department of Applied Mathematics and Theoretical Physics, where he leads a group of ACT researchers. “It looks just as our theories predict.”

Although dark matter makes up a large chunk of the universe and shaped its evolution, it has remained hard to detect because it doesn’t interact with light or other forms of electromagnetic radiation. As far as we know, dark matter only interacts with gravity.

To track it down, the more than 160 collaborators who have built and gathered data from the National Science Foundation’s Atacama Cosmology Telescope in the high Chilean Andes observe light emanating following the dawn of the universe’s formation, the Big Bang—when the universe was only 380,000 years old. Cosmologists often refer to this diffuse light that fills our entire universe as the “baby picture of the universe,” but formally, it is known as the cosmic microwave background radiation (CMB).

̽��ֱ��team tracks how the gravitational pull of large, heavy structures including dark matter warps the CMB on its 14-billion year journey to us, like how a magnifying glass bends light as it passes through its lens.

“We’ve made a new mass map using distortions of light left over from the Big Bang,” said Mathew Madhavacheril from the ̽��ֱ�� of Pennsylvania, lead author of one of the papers. “Remarkably, it provides measurements that show that both the ‘lumpiness’ of the universe, and the rate at which it is growing after 14 billion years of evolution, are just what you’d expect from our standard model of cosmology based on Einstein's theory of gravity.”

“Our results also provide new insights into an ongoing debate some have called ‘ ̽��ֱ��Crisis in Cosmology’,” said Sherwin. This crisis stems from recent measurements that use a different background light, one emitted from stars in galaxies rather than the CMB. These have produced results that suggest the dark matter was not lumpy enough under the standard model of cosmology and led to concerns that the model may be broken. However, the team’s latest results from ACT were able to precisely assess that the vast lumps seen in this image are the exact right size.

“When I first saw them, our measurements were in such good agreement with the underlying theory that it took me a moment to process the results,” said Cambridge PhD candidate Frank Qu, lead author of one of the new papers. “But we still don’t know what the dark matter is, so it will be interesting to see how this possible discrepancy between different measurements will be resolved.”

“ ̽��ֱ��CMB lensing data rivals more conventional surveys of the visible light from galaxies in their ability to trace the sum of what is out there,” said Suzanne Staggs from Princeton ̽��ֱ��, Director of ACT. “Together, the CMB lensing and the best optical surveys are clarifying the evolution of all the mass in the universe.”

“When we proposed this experiment in 2003, this measurement wasn’t even on our agenda; we had no idea the full extent of information that could be extracted from our telescope,” said Mark Devlin, from the ̽��ֱ�� of Pennsylvania, Deputy Director of ACT. “We owe this to the cleverness of the theorists, the many people who built new instruments to make our telescope more sensitive, and the new analysis techniques our team came up with.”

With ACT having been decommissioned in late 2022, further papers highlighting some of the other final results are slated for submission in the coming year. Observations will continue at the site with the Simons Observatory, including a new telescope due to begin in 2024 that can map the sky almost ten times faster.

̽��ֱ��pre-print articles highlighted in this release are available on act.princeton.edu and will appear on the open-access arXiv.org. They have been submitted to ̽��ֱ��Astrophysical Journal.

This work was supported by the U.S. National Science Foundation, Princeton ̽��ֱ��, the ̽��ֱ�� of Pennsylvania, and a Canada Foundation for Innovation award. Team members at the ̽��ֱ�� of Cambridge were supported by the European Research Council.

A new image reveals the most detailed map of dark matter distributed across a quarter of the entire sky, reaching deep into the cosmos.

We have mapped the invisible dark matter across the sky to the largest distances, and clearly see features of this invisible world that are hundreds of millions of light-years across

Blake Sherwin

ACT Collaboration

A new map of the dark matter made by the Atacama Cosmology Telescope. ̽��ֱ��orange regions show where there is more mass; purple where there is less.

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

A whole host of options

cjb250 — Fri, 09 Oct 2015 08:30:04 +0000

Professor Lalita Ramakrishnan is, it’s fair to say, a world authority on the biology of TB. She studies the disease – one which most people will know of as a disease of the lungs – using what at first sight seems an unusual model: the zebrafish.

“What most people don’t realise is that about 40% of human TB occurs outside the lungs,” explains Ramakrishnan. “It can infect the brain, bone, heart, reproductive organs, skin, even the ear. In fact, TB infection is a basic biology question, and this is the same in zebrafish as it is in humans.”

TB is caused by Mycobacterium tuberculosis, which is generally transmitted from person to person through the air. It has been around since at least the Neolithic period, but its prevalence in 19th-century literature led it to be considered something of a ‘romantic’ disease. ̽��ֱ��truth is a long way from this portrayal. ̽��ֱ��disease can cause breathlessness, wasting and eventual death. And while treatments do exist, the drug regimen is one of the longest for any curable disease: a patient will typically need to take medication for six months.

Ramakrishnan is involved in a new trial due to start soon that might allow doctors to reduce the length of this treatment. She is cautiously optimistic that it can be reduced to four months; if successful, however, it may eventually lead to treatments more on a par with standard antibiotic treatments of a couple of weeks.

̽��ֱ��trial builds on work in zebrafish carried out by Ramakrishnan and colleagues at the ̽��ֱ�� of Washington, Seattle, before she moved to the Department of Medicine in Cambridge in September 2014. These small fish, which grow to the length of a little finger, helped her and collaborator Professor Paul Edelstein from the ̽��ֱ�� of Pennsylvania (currently on sabbatical in Cambridge) to make an important discovery that could explain why it takes a six-month course of antibiotics to rid the body of the disease (rather than seven to ten days that most infections take) and yet in the lab can easily be killed.

Within our bodies, we have a host of specialist immune cells that fight infection. One of these is the macrophage (Greek for ‘big eater’). This cell engulfs the TB bacterium and tries to break it down. This, together with powerful antibiotics, should make eliminating TB from the body a cinch. Ramakrishnan’s breakthrough was to show why this wasn’t the case: once inside the macrophages, TB switches on pumps, known as ‘efflux pumps’. Anything that we throw at it, it just pumps back out again.

“Once we’d identified the pumps, we started to look for drugs that are out there in the market and tested a few of them,” she explains. “We found that verapamil, an old drug, made the bacteria susceptible to two of the antibiotics we use to fight TB.”

̽��ֱ��trial of verapamil, which is commonly used to treat high blood pressure, is due to start soon at the National Institute for Research in Tuberculosis (NIRT) in Chennai, India.

Ramakrishnan is one of a number of brilliant minds working as part of a collaboration between the NIRT and the ̽��ֱ�� of Cambridge to apply the very latest in scientific thinking and technology to the problem of TB.

An expansion of this collaboration has now become possible through the recent award of a £2 million joint grant from the UK Medical Research Council (MRC) and the Department of Biotechnology (DBT) in India, which will enable the exchange of British and Indian researchers. For Professor Sharon Peacock, the UK lead on the proposal, this means an opportunity to train a new cohort of early-career researchers in an environment where they will have access to outstanding scientific facilities and training, at the same time as becoming familiar with the clinical face and consequences of TB for people in India.

“India is home to a large pool of talented young people with the potential to help fight back against this deadly disease,” says Peacock. “Developing a close collaboration between Cambridge and Chennai involving two-way traffic of scientists and ideas is an exciting opportunity to start to tap into this.”

There are few places more suitable for the proposed work than India. According to the World Health Organization, India is home to almost one in four of all worldwide cases of TB, with over two million newly diagnosed cases in 2014.

Not only that, but it is one of the countries that has seen an increase in the number of cases of drug resistance to TB – including ‘multi-drug’-resistant, and even more worrying, ‘extremely’ drug-resistant strains of TB against which none of our first- and second-line drug treatments work. In part, this increase reflects improved access to diagnostic services, but the situation highlights why new approaches to tackling the disease are urgently needed, says Professor Soumya Swaminathan, Director of NIRT and the India lead in the collaboration.

“So far, the treatment of TB has focused almost exclusively on using drugs to try to kill the bacteria directly, but there’s increasing evidence that there may be benefits to targeting the host. TB is very clever and it manipulates the host immune system to its own advantage, so if we could use drugs to help the immune system, then we may be able to make it more effective.”

This is the approach that Professors Ken Smith and Andres Floto from the Department of Medicine at Cambridge, also part of the collaboration, are taking. Smith is looking at the role that specialist immune cells known as T cells play in the persistence of multi-drug-resistant strains of TB. His group has evidence that around two thirds of the population have T cells which have a tendency to become ‘exhausted’ when activated.

“It might be that exhausted T cells can’t fight multi-drug-resistant TB effectively, in which case we need to find a way to overcome this exhaustion and spur the T cells on to rid the body of the disease,” says Smith.

For Floto, the key may lie in the role played by the macrophages and their otherwise voracious appetites. As their Greek name suggests, macrophages ‘eat’ unwanted material (surprisingly similar in action to Pac-Man), effectively chewing it up, breaking it down and spitting it out again.

This process, known as autophagy (‘self-eating’), is a repair mechanism for clearing damaged bits of cells and recycling them for future use, but also works as a defence mechanism against some invading bacteria. So why, when it engulfs TB, does the bacterium manage to avoid being digested?

“Autophagy is partially inhibited by TB itself, but we found that if you overstimulate this mechanism – like flooring the accelerator of a car – you can overcome the bacteria,” explains Floto. “Clearly this will be applicable to normal TB, but we already have drugs that are effective against this. We want to know if this would work against multi-drug-resistant strains.”

Floto and colleagues already have a list of potential drugs that can stimulate autophagy, drugs that have already been licensed and are in use to treat other conditions, such as carbamazepine, which is used to treat epileptic seizures. These drugs are safe to use: the question is, will they work against TB?

“We’ve already shown that carbamazepine stimulates autophagy in cells to kill TB – even multi-drug-resistant TB. We now want to refine it and test it in mice and in fish, alongside a shortlist of around 30 other potential drugs,” he adds.

TB evolves through ‘polymorphisms’ – spontaneous changes in the letters of its DNA to create variants. Because the drug regimen to fight the disease lasts so long, many patients do not take the full course of their medicines. If the TB is allowed to relapse, it can evolve drug resistance.

These patterns of resistance can be detected using genome sequencing – reading the DNA of the bacteria. Peacock believes this technique may be able to help doctors more easily diagnose drug resistance in patients.

“TB is very slow to grow in the laboratory, which means that testing an organism to confirm which antibiotics it is susceptible or resistant to can take several weeks, especially in the case of more resistant strains,” she says. “There is increasing evidence that antibiotic resistance can be predicted from the genome sequence of the organism, and we want to establish and evaluate this technology in India, where it is needed.”

This sequencing data could also then help inform the search for new drugs, explains Professor Sir Tom Blundell from the Department of Biochemistry. He is no stranger to TB: his grandfather died from the disease shortly after the war – though, as Blundell points out, this strain of TB is far less common now, as the organism has evolved in different communities throughout the world.

“We can take the polymorphisms and ask questions such as ‘What does this mean for the use of current drugs?’” says Blundell. “ ̽��ֱ��nature of the polymorphisms in the TB genome sequence of an infected individual can give us information on where that person was infected and what are the drugs that might be most effective. We can then begin to look at new targets for particular polymorphisms.”

Blundell plans to take the information gathered through the Chennai partnership and feed it into his drug discovery work. He takes a structural approach to solving the problem: look at the shape of the polymorphism and its protein products and try to find small molecules that can attach to and manipulate them. In essence, it’s akin to picking a lock by analysing the shape of its mechanism and trying to identify a key that could turn it, thus opening the door.

Yet even if the Chennai venture is successful, and research from the partnership leads to a revolution in how we understand and treat TB, the team recognise that this is unlikely to be enough to eradicate the disease for good.

“TB is as much a public health issue as one of infectious diseases,” says Ramakrishnan, pointing to Europe, where even before the introduction of antibiotics, the disease was already on the decline. “We need better nutrition, better air, less smoking, reductions in diabetes.”

Swaminathan agrees. “TB is very much associated with poverty and all the risk factors that go with it,” she says. “When people are living in very crowded conditions, when they’re malnourished, TB is going to continue to spread. This is happening in the slums of Mumbai, for example, where we’re seeing a mini-epidemic of multi-drug-resistant TB. Unless we see a rapid improvement in the living standards of people we’re not going to see a very major effect. There’s only so much we can do biomedically.”

Inset image: Macrophage engulfing Tuberculosis pathogen (ZEISS Microscopy).

Almost one in four of the world’s cases of tuberculosis (TB) are in India and the disease is constantly adapting itself to outwit our medicines. Could the answer lie in targeting not the bacteria but its host, the patient?

What most people don’t realise is that about 40% of human TB occurs outside the lungs ... It can infect the brain, bone, heart, reproductive organs, skin, even the ear

Lalita Ramakrishnan

Calcutta Rescue

Picture to educate people in villages that have no medical service about the spread of TB

̽��ֱ��Next Generation

If there’s one thing on the side of science v. TB, it’s the wealth of talent available in India.

Professor Sir Tom Blundell is quick to praise the Indian postdocs that come to work in his lab. “They tend to be naturally very inquisitive and interactive, with very enquiring minds,” he says.

This is something with which Professor Ashok Venkitaraman, Director of the Medical Research Council (MRC) Cancer Unit at Cambridge, wholeheartedly agrees. He has helped establish the Center for Chemical Biology and Therapeutics (CCBT) in Bangalore in part, he says, because “the number of really bright, well-trained young scientists in India is huge. ̽��ֱ��level of enthusiasm and commitment is something I find quite exceptional.”

̽��ֱ��CCBT is an inter-institutional centre that links the Institute for Stem Cell Biology and Regenerative Medicine and the National Center for Biological Sciences, both of which are world-class Indian research institutes studying fundamental biology. However, argues Venkitaraman, India needs the capacity to translate fundamental research to clinical application.

It is to help bridge this gap that the CCBT was established, with funding from the Department of Biotechnology (DBT) in India, recently supplemented by a £2 million joint award from the UK MRC and the DBT. ̽��ֱ��idea is to find innovative ways to discover ‘next-generation’ medicines against human diseases, by coupling biological research that reveals novel drug targets with approaches in chemistry and structural biology that create potential drug candidates.

Although Venkitaraman’s interest is in cancer, he predicts the work of the CCBT will be “disease agnostic”, because similar types of novel drug targets have been implicated in infectious diseases, cancer and even developmental defects.

“We desperately need to develop new medicines not just for currently problematic diseases like cancer and TB, but also for the new challenges that are being thrown at us all the time – antibiotic resistance, new infections, metabolic syndromes and diseases of ageing, for example. Nowhere is this need more critical than in emerging nations like India where the spectrum of disease is distinct from countries like the UK.”

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Licence type:

Attribution-Noncommercial-ShareAlike