伊坎大楼前的AJ te Velthuis

为什么有些病毒是无害的,而有些则是致命的? A.J. te Velthuis正在调查这个案子.

1月. 10, 2022, 12:15 p.m.

A.J. te Velthuis, 分子生物学的助理教授, 为什么大多数病毒是无害的,而其他病毒却能导致严重的疾病.

病毒的数量是人类的400万亿倍,然而大流行却很罕见. 为什么? 为什么 do a few viruses inflict so much dam年龄, when the vast majority are harmless or even helpful?

这些问题驱动 A.J. te Velthuis他是一名病毒学家,于2021年1月加入beplay官网app下载的分子生物学教员.

“AJ是病毒学的未来,”他说 邦妮Bassler他是Squibb分子生物学教授和系主任. “beplay体育部门在病毒学方面一直是一个强大的部门. 当beplay体育要请一位新助理教授的时候, our senior virologists — an incredible group of scholars and intellects — helped us understand where the future of this field is going, 他们找到了他.”

“我研究RNA病毒,我已经做了很长时间了,”te Velthuis说. “我对为什么有些新病毒特别感兴趣, 当它们跳到人类身上时, 突然引发严重疾病, 而当它们在蝙蝠或其他物种身上时, 它们看起来几乎是无害的.”

He studies the fundamental mechanisms for how viruses replicate and confuse our immune systems. 他还在研究灭活病毒的新口罩, 阻止病毒复制的抗病毒药物, and how variants of the same virus — such as Omicron or Delta — can arise and cause more harm than others. 他指出了世界各地的疫苗接种项目所发挥的关键作用.

“Unvaccinated people are acting as a reservoir from which the virus causing COVID-19 can keep jumping back into vaccinated people,Velthuis说. “不幸的是,这是一个完美的新变种选择模型.”

称的冠状病毒

在大流行初期, 研究人员对SARS-CoV-2的活体样本进行了实验, 导致COVID-19的病毒, 冒着极大的个人风险. Te Velthuis found a way to change that — to edit the genome of the new SARS strain so that he and his colleagues around the world could study the virus 与out exposing themselves and their loved ones to the deadly disease.

这样做, 他利用了这是一种异常复杂的病毒这一事实, 与 an elaborate blueprint coded in a long sequence of RNA (the single-stranded cousin of DNA).

长基因组可以想象成一列火车, 有一个火车头和后面连在一起的一长串汽车. 当病毒想要向细胞发出指令时,它就入侵了, 它需要突出其基因组中最相关的部分, 所以它把“火车车厢”拼接起来,重新连接到前面. The researchers in te Velthuis’ lab used that property to isolate one locomotive and one train car, resulting in a micro-virus that cannot infect new cells but can still be useful for testing antiviral treatments and studying new mutations.

“它不再致命了, 因为你需要所有其他的“车厢”来创建一个完整的, 传染性病毒粒子,韦尔修斯说. “如果你只有一节单独的火车车厢, 它不能产生任何传染性的东西, 但它能告诉你轮子是如何工作的, 机车多么结实啊.”

孩子们的手在玩玩具火车

在大流行早期, 研究人员冒着极大的个人风险对病毒的活标本进行实验. Te Velthuis found a way to change that — to edit the genome of the new SARS strain so that he and his colleagues around the world could study the virus 与out exposing themselves and their loved ones to the deadly disease. SARS-CoV-2, 导致COVID-19的病毒, 有一个很长的RNA基因组,可以被认为是一个序列, 有一个火车头和一长串汽车. 当病毒想要向细胞发出指令时,它就入侵了, 它将相关的“火车车厢”拼接起来,并将其重新安装在前面. Te Velthuis和他的团队利用这片土地隔离了一个火车头和一节车厢, creating a micro-virus that cannot infect new cells but can still be useful for testing anti-COVID treatments and studying new mutations. “它不再致命了, 因为你需要所有其他的“车厢”来创建一个完整的, 传染性病毒粒子,韦尔修斯说.

在许多方面, te Velthuis像工程师一样思考, 他说那是来自满是建筑玩具的童年. “Structural biology has advanced in such a way that you can start to look at molecules almost like Legos in how they fit together and how we can build 与 them. 它让思考、画和教学生这些东西变得很有趣. 它是如此视觉化,如此,如此美丽.”

对这些微小结构的热爱是吸引他来到beplay体育的部分原因, 它拥有非凡的显微镜研究人员群体. “An im年龄 tells so much more than some of the biochemical work that we do — both to scientists and when communicating 与 students and the wider community,Velthuis说. “So getting to work 与 them and finding new ways to look at viruses is really inspiring.”

He arrived at Princeton in 1月uary 2021 to find a mountain of boxed equipment and a construction zone where his lab should be. 他已经有一个研究生了, 金伯利Sabsay他的顾问之一 Ned Wingreenbeplay体育(Princeton)的霍华德. 生命科学的前任教授, who is also a professor of molecular biology and the Lewis-Sigler Institute for Integrative Genomics.

Sabsay和te Velthuis在从零开始建造实验室的过程中经历了挣扎和快乐, 尽管与covid - 19相关的建设延误和供应挑战.

“打开装着新设备的箱子感觉就像过圣诞节, 这让beplay体育在一次又一次的拖延中保持清醒,”Sabsay说. “我和A一对一工作的经历.J. 设计和组装他的梦想实验室,是无价的. 这个过程极其缓慢, 充满挫折和失败, but it ultimately proved to be more rewarding than I could have ever imagined — much like science itself.”

金伯利Sabsay和Karishma Bisht在实验室工作

Graduate student 金伯利Sabsay (left) and postdoctoral research associate Karishma Bisht work 与 te Velthuis to discover how viruses replicate and how they disrupt the immune system, 导致事态失控.

用棉签来预测肺炎?

早在当前大流行之前, te Velthuis研究了冠状病毒和各种流感病毒株, comparing a seasonal flu (H1N1) 与 two pandemics: the 1918 flu and the avian flu (H5N1). 而季节性流感的症状通常比较轻微, the other two flus can trigger an overreaction from the immune system that fills the lungs 与 fluid (pneumonia). 正如世界在2020年初认识到的那样, the coronavirus family of viruses has a similar pattern: While most coronaviruses only cause mild cold symptoms, 有些会引起肺炎, 包括SARS-CoV-2.

Te Velthuis and his team found that the molecular trigger that turns the flu into pneumonia is a tiny viral RNA molecule. 他们可以在体外检测到, 在1918年感染流感的雪貂身上, and in saliva swabs from hospital patients; continued research, te Velthuis希望, 会导致一种快速检测来预测严重流感吗, 最终得到更快更好的治疗.

他还想更进一步. 他的团队现在正致力于发现这种触发背后的机制, 他们的目标是找到抑制这一过程的药物, 把严重的健康威胁变成轻微的不便.

“如果beplay体育有一个工具, 比如一种药物, 当致病性病毒出现时,beplay体育可以使用它, beplay体育可以立即把它变成一种更容易控制的季节性病毒, beplay体育也不会看到医院和其他医疗机构承受那么大的压力,Velthuis说, 他的研究是由美国国立卫生研究院资助的. 这是更大的梦想,更大的目标.”

教师和研究人员

今年春天, te Velthuis将教授“病原体”, 《beplay体育》的作者是卡梅隆·梅尔沃德, 也是分子生物学的助理教授.

这门课程将从多个角度研究流行病,te Velthuis说. “如何研究病毒? 你如何找到保护自己的方法? 病毒需要什么才能进入细胞? 是什么让它们致病的? 是什么导致了流行病?”

病毒 彼此之间有很大的不同吗, 但他们都要解决同样的问题, te Velthuis解释说——进入细胞, 蛋白质相互作用, 逃避免疫防御——这意味着病毒通常使用类似的机制. 这就是为什么他对加入beplay官网app下载的研究界如此兴奋的部分原因. 该病毒试图解决工程问题,因为它在不同环境之间跳跃, 所以听听物理学家和工程师是如何思考这些问题的真的很有帮助,”他说.

It’s no coincidence that Princeton’s two newest coronavirus researchers are teaching a course on pandemics, 当然.

在分子生物学系, beplay体育重视成为优秀教师, 这种角色的每一种表现——在教室里, 在实验室里, 论文的学生,”Bassler说, 部门的椅子. “在beplay体育部门, 许多学生成为已发表论文的共同作者, 因为他们在毕业论文中有重要发现. beplay官网app下载分子生物系的学生研究是真实的. We have total immersion in research and in the thrill of discovery — we don't kid around about that here.”

A.J. 让beplay体育可以自由地做最狂野的实验梦,”Sabsay说, 谁继续在他的实验室. 当beplay体育疯狂的计划导致beplay体育失败时, he is right there 与 us to help resuscitate them and keep our fantasy alive for as long as possible.”

“A.J. 从来不会拒绝任何我想尝试的事情。 Elizaveta Elshina, who was his first graduate student and came 与 te Velthuis from Cambridge University.

“科学就是要尝试不同的东西,”他说 Karishma Bisht他于2021年秋季加入了他的实验室. “并不是每件事都能成功,但是除非你去尝试,否则你不会知道—— and AJ is willing to take the risk 与 you to explore these scientific questions by sharing his knowledge, 专门知识和资源.”

Bassler said that te Velthuis has already made himself a valuable addition to his many communities of researchers — 与in his lab, 在他们的部门, 以及整个大学. “因为beplay体育对教学的承诺, Princeton self-selects for people who believe that part of the social contract of the scientist is to teach the next generation of scientists to be scientists,”她说. ”和.J. 对beplay体育部门的合作有帮助吗, “人人为我,我为人人”的精神.这发生得很快,尤其是考虑到新冠肺炎的限制. 让自己沉浸在Zoom的一个部门里很难,但他做到了.”